diff --git "a/meta/bib.txt" "b/meta/bib.txt" new file mode 100644--- /dev/null +++ "b/meta/bib.txt" @@ -0,0 +1,4410 @@ +@ARTICLE{Ji2020-dp, + title = "Multimodal analysis of composition and spatial architecture in + human squamous cell carcinoma", + author = "Ji, Andrew L and Rubin, Adam J and Thrane, Kim and Jiang, Sizun + and Reynolds, David L and Meyers, Robin M and Guo, Margaret G + and George, Benson M and Mollbrink, Annelie and + Bergenstr{\aa}hle, Joseph and Larsson, Ludvig and Bai, Yunhao + and Zhu, Bokai and Bhaduri, Aparna and Meyers, Jordan M and + Rovira-Clav{\'e}, Xavier and Hollmig, S Tyler and Aasi, Sumaira + Z and Nolan, Garry P and Lundeberg, Joakim and Khavari, Paul A", + abstract = "To define the cellular composition and architecture of cutaneous + squamous cell carcinoma (cSCC), we combined single-cell RNA + sequencing with spatial transcriptomics and multiplexed ion beam + imaging from a series of human cSCCs and matched normal skin. + cSCC exhibited four tumor subpopulations, three recapitulating + normal epidermal states, and a tumor-specific keratinocyte (TSK) + population unique to cancer, which localized to a fibrovascular + niche. Integration of single-cell and spatial data mapped + ligand-receptor networks to specific cell types, revealing TSK + cells as a hub for intercellular communication. Multiple + features of potential immunosuppression were observed, including + T regulatory cell (Treg) co-localization with CD8 T cells in + compartmentalized tumor stroma. Finally, single-cell + characterization of human tumor xenografts and in vivo CRISPR + screens identified essential roles for specific tumor + subpopulation-enriched gene networks in tumorigenesis. These + data define cSCC tumor and stromal cell subpopulations, the + spatial niches where they interact, and the communicating gene + networks that they engage in cancer.", + journal = "Cell", + publisher = "Elsevier BV", + volume = 182, + number = 2, + pages = "497--514.e22", + month = jul, + year = 2020, + keywords = "CRISPR screen; MIBI; intra-tumoral heterogeneity; multi-omics; + scRNA-seq; skin cancer; spatial transcriptomics; squamous cell + carcinoma; tumor immunology; tumor microenvironment", + copyright = "http://creativecommons.org/licenses/by/4.0/", + language = "en" +} + +@ARTICLE{Chen2023-zm, + title = "{STmut}: a framework for visualizing somatic alterations in + spatial transcriptomics data of cancer", + author = "Chen, Limin and Chang, Darwin and Tandukar, Bishal and + Deivendran, Delahny and Pozniak, Joanna and Cruz-Pacheco, Noel + and Cho, Raymond J and Cheng, Jeffrey and Yeh, Iwei and Marine, + Chris and Bastian, Boris C and Ji, Andrew L and Shain, A Hunter", + abstract = "Spatial transcriptomic technologies, such as the Visium platform, + measure gene expression in different regions of tissues. Here, we + describe new software, STmut, to visualize somatic point + mutations, allelic imbalance, and copy number alterations in + Visium data. STmut is tested on fresh-frozen Visium data, + formalin-fixed paraffin-embedded (FFPE) Visium data, and tumors + with and without matching DNA sequencing data. Copy number is + inferred on all conditions, but the chemistry of the FFPE + platform does not permit analyses of single nucleotide variants. + Taken together, we propose solutions to add the genetic dimension + to spatial transcriptomic data and describe the limitations of + different datatypes.", + journal = "Genome Biol.", + volume = 24, + number = 1, + pages = "273", + month = nov, + year = 2023, + language = "en" +} + +@ARTICLE{Andersson2021-nr, + title = "Spatial deconvolution of {HER2-positive} breast cancer + delineates tumor-associated cell type interactions", + author = "Andersson, Alma and Larsson, Ludvig and Stenbeck, Linnea and + Salm{\'e}n, Fredrik and Ehinger, Anna and Wu, Sunny Z and + Al-Eryani, Ghamdan and Roden, Daniel and Swarbrick, Alex and + Borg, {\AA}ke and Fris{\'e}n, Jonas and Engblom, Camilla and + Lundeberg, Joakim", + abstract = "In the past decades, transcriptomic studies have revolutionized + cancer treatment and diagnosis. However, tumor sequencing + strategies typically result in loss of spatial information, + critical to understand cell interactions and their functional + relevance. To address this, we investigate spatial gene + expression in HER2-positive breast tumors using Spatial + Transcriptomics technology. We show that expression-based + clustering enables data-driven tumor annotation and assessment + of intra- and interpatient heterogeneity; from which we discover + shared gene signatures for immune and tumor processes. By + integration with single cell data, we spatially map + tumor-associated cell types to find tertiary lymphoid-like + structures, and a type I interferon response overlapping with + regions of T-cell and macrophage subset colocalization. We + construct a predictive model to infer presence of tertiary + lymphoid-like structures, applicable across tissue types and + technical platforms. Taken together, we combine different data + modalities to define a high resolution map of cellular + interactions in tumors and provide tools generalizing across + tissues and diseases.", + journal = "Nat. Commun.", + publisher = "Springer Science and Business Media LLC", + volume = 12, + number = 1, + pages = "6012", + month = oct, + year = 2021, + copyright = "https://creativecommons.org/licenses/by/4.0", + language = "en" +} + +% The entry below contains non-ASCII chars that could not be converted +% to a LaTeX equivalent. +@ARTICLE{He2020-de, + title = "Integrating spatial gene expression and breast tumour morphology + via deep learning", + author = "He, Bryan and Bergenstr{\aa}hle, Ludvig and Stenbeck, Linnea and + Abid, Abubakar and Andersson, Alma and Borg, {\AA}ke and + Maaskola, Jonas and Lundeberg, Joakim and Zou, James", + abstract = "Spatial transcriptomics allows for the measurement of RNA + abundance at a high spatial resolution, making it possible to + systematically link the morphology of cellular neighbourhoods + and spatially localized gene expression. Here, we report the + development of a deep learning algorithm for the prediction of + local gene expression from haematoxylin-and-eosin-stained + histopathology images using a new dataset of 30,612 spatially + resolved gene expression data matched to histopathology images + from 23 patients with breast cancer. We identified over 100 + genes, including known breast cancer biomarkers of intratumoral + heterogeneity and the co-localization of tumour growth and + immune activation, the expression of which can be predicted from + the histopathology images at a resolution of 100 µm. We also + show that the algorithm generalizes well to The Cancer Genome + Atlas and to other breast cancer gene expression datasets + without the need for re-training. Predicting the spatially + resolved transcriptome of a tissue directly from tissue images + may enable image-based screening for molecular biomarkers with + spatial variation.", + journal = "Nat. Biomed. Eng.", + publisher = "Springer Science and Business Media LLC", + volume = 4, + number = 8, + pages = "827--834", + month = aug, + year = 2020, + copyright = "https://www.springernature.com/gp/researchers/text-and-data-mining", + language = "en" +} + +@ARTICLE{Stahl2016-zf, + title = "Visualization and analysis of gene expression in tissue sections + by spatial transcriptomics", + author = "St{\aa}hl, Patrik L and Salm{\'e}n, Fredrik and Vickovic, Sanja + and Lundmark, Anna and Navarro, Jos{\'e} Fern{\'a}ndez and + Magnusson, Jens and Giacomello, Stefania and Asp, Michaela and + Westholm, Jakub O and Huss, Mikael and Mollbrink, Annelie and + Linnarsson, Sten and Codeluppi, Simone and Borg, {\AA}ke and + Pont{\'e}n, Fredrik and Costea, Paul Igor and Sahl{\'e}n, Pelin + and Mulder, Jan and Bergmann, Olaf and Lundeberg, Joakim and + Fris{\'e}n, Jonas", + abstract = "Spatial structure of RNA expression RNA-seq and similar methods + can record gene expression within and among cells. Current + methods typically lose positional information and many require + arduous single-cell isolation and sequencing. St{\aa}hl et al. + have developed a way of measuring the spatial distribution of + transcripts by annealing fixed brain or cancer tissue samples + directly to bar-coded reverse transcriptase primers, performing + reverse transcription followed by sequencing and computational + reconstruction, and they can do so for multiple genes. Science , + this issue p. 78", + journal = "Science", + publisher = "American Association for the Advancement of Science (AAAS)", + volume = 353, + number = 6294, + pages = "78--82", + month = jul, + year = 2016, + copyright = "http://www.sciencemag.org/about/science-licenses-journal-article-reuse", + language = "en" +} + +@ARTICLE{Asp2019-ga, + title = "A spatiotemporal organ-wide gene expression and cell atlas of + the developing human heart", + author = "Asp, Michaela and Giacomello, Stefania and Larsson, Ludvig and + Wu, Chenglin and F{\"u}rth, Daniel and Qian, Xiaoyan and + W{\"a}rdell, Eva and Custodio, Joaquin and Reimeg{\aa}rd, Johan + and Salm{\'e}n, Fredrik and {\"O}sterholm, Cecilia and + St{\aa}hl, Patrik L and Sundstr{\"o}m, Erik and {\AA}kesson, + Elisabet and Bergmann, Olaf and Bienko, Magda and + M{\aa}nsson-Broberg, Agneta and Nilsson, Mats and Sylv{\'e}n, + Christer and Lundeberg, Joakim", + abstract = "The process of cardiac morphogenesis in humans is incompletely + understood. Its full characterization requires a deep + exploration of the organ-wide orchestration of gene expression + with a single-cell spatial resolution. Here, we present a + molecular approach that reveals the comprehensive + transcriptional landscape of cell types populating the embryonic + heart at three developmental stages and that maps + cell-type-specific gene expression to specific anatomical + domains. Spatial transcriptomics identified unique gene profiles + that correspond to distinct anatomical regions in each + developmental stage. Human embryonic cardiac cell types + identified by single-cell RNA sequencing confirmed and enriched + the spatial annotation of embryonic cardiac gene expression. In + situ sequencing was then used to refine these results and create + a spatial subcellular map for the three developmental phases. + Finally, we generated a publicly available web resource of the + human developing heart to facilitate future studies on human + cardiogenesis.", + journal = "Cell", + publisher = "Elsevier BV", + volume = 179, + number = 7, + pages = "1647--1660.e19", + month = dec, + year = 2019, + keywords = "gene expression; heart development; human development; human + developmental cell atlas; in situ sequencing; single-cell + RNA-sequencing; spatial transcriptomics; spatially resolved + transcriptomics", + copyright = "http://www.elsevier.com/open-access/userlicense/1.0/", + language = "en" +} + +@ARTICLE{Hasel2021-pg, + title = "Neuroinflammatory astrocyte subtypes in the mouse brain", + author = "Hasel, Philip and Rose, Indigo V L and Sadick, Jessica S and + Kim, Rachel D and Liddelow, Shane A", + abstract = "Astrocytes undergo an inflammatory transition after infections, + acute injuries and chronic neurodegenerative diseases. How this + transition is affected by time and sex, its heterogeneity at the + single-cell level and how sub-states are spatially distributed + in the brain remains unclear. In this study, we investigated + transcriptome changes of mouse cortical astrocytes after an + acute inflammatory stimulus using the bacterial cell wall + endotoxin lipopolysaccharide. We identified fast transcriptomic + changes in astrocytes occurring within hours that drastically + change over time. By sequencing ~80,000 astrocytes at + single-cell resolution, we show that inflammation causes a + widespread response with subtypes of astrocytes undergoing + distinct inflammatory transitions with defined transcriptomic + profiles. We also attribute key sub-states of + inflammation-induced reactive astrocytes to specific brain + regions using spatial transcriptomics and in situ hybridization. + Together, our datasets provide a powerful resource for profiling + astrocyte heterogeneity and will be useful for understanding the + biological importance of regionally constrained reactive + astrocyte sub-states.", + journal = "Nat. Neurosci.", + publisher = "Springer Science and Business Media LLC", + volume = 24, + number = 10, + pages = "1475--1487", + month = oct, + year = 2021, + copyright = "https://www.springernature.com/gp/researchers/text-and-data-mining", + language = "en" +} + +@ARTICLE{Ratz2022-fl, + title = "Clonal relations in the mouse brain revealed by single-cell and + spatial transcriptomics", + author = "Ratz, Michael and von Berlin, Leonie and Larsson, Ludvig and + Martin, Marcel and Westholm, Jakub Orzechowski and La Manno, + Gioele and Lundeberg, Joakim and Fris{\'e}n, Jonas", + abstract = "The mammalian brain contains many specialized cells that develop + from a thin sheet of neuroepithelial progenitor cells. + Single-cell transcriptomics revealed hundreds of molecularly + diverse cell types in the nervous system, but the lineage + relationships between mature cell types and progenitor cells are + not well understood. Here we show in vivo barcoding of early + progenitors to simultaneously profile cell phenotypes and clonal + relations in the mouse brain using single-cell and spatial + transcriptomics. By reconstructing thousands of clones, we + discovered fate-restricted progenitor cells in the mouse + hippocampal neuroepithelium and show that microglia are derived + from few primitive myeloid precursors that massively expand to + generate widely dispersed progeny. We combined spatial + transcriptomics with clonal barcoding and disentangled migration + patterns of clonally related cells in densely labeled tissue + sections. Our approach enables high-throughput dense + reconstruction of cell phenotypes and clonal relations at the + single-cell and tissue level in individual animals and provides + an integrated approach for understanding tissue architecture.", + journal = "Nat. Neurosci.", + publisher = "Springer Science and Business Media LLC", + volume = 25, + number = 3, + pages = "285--294", + month = mar, + year = 2022, + copyright = "https://creativecommons.org/licenses/by/4.0", + language = "en" +} + +@ARTICLE{Lebrigand2023-im, + title = "The spatial landscape of gene expression isoforms in tissue + sections", + author = "Lebrigand, Kevin and Bergenstr{\aa}hle, Joseph and Thrane, Kim + and Mollbrink, Annelie and Meletis, Konstantinos and Barbry, + Pascal and Waldmann, Rainer and Lundeberg, Joakim", + abstract = "In situ capturing technologies add tissue context to gene + expression data, with the potential of providing a greater + understanding of complex biological systems. However, splicing + variants and full-length sequence heterogeneity cannot be + characterized at spatial resolution with current transcriptome + profiling methods. To that end, we introduce spatial isoform + transcriptomics (SiT), an explorative method for characterizing + spatial isoform variation and sequence heterogeneity using + long-read sequencing. We show in mouse brain how SiT can be used + to profile isoform expression and sequence heterogeneity in + different areas of the tissue. SiT reveals regional isoform + switching of Plp1 gene between different layers of the olfactory + bulb, and the use of external single-cell data allows the + nomination of cell types expressing each isoform. Furthermore, + SiT identifies differential isoform usage for several major + genes implicated in brain function (Snap25, Bin1, Gnas) that are + independently validated by in situ sequencing. SiT also provides + for the first time an in-depth A-to-I RNA editing map of the + adult mouse brain. Data exploration can be performed through an + online resource (https://www.isomics.eu), where isoform + expression and RNA editing can be visualized in a spatial + context.", + journal = "Nucleic Acids Res.", + publisher = "Oxford University Press (OUP)", + volume = 51, + number = 8, + pages = "e47", + month = may, + year = 2023, + copyright = "https://creativecommons.org/licenses/by-nc/4.0/", + language = "en" +} + +@ARTICLE{Joglekar2021-xs, + title = "A spatially resolved brain region- and cell type-specific + isoform atlas of the postnatal mouse brain", + author = "Joglekar, Anoushka and Prjibelski, Andrey and Mahfouz, Ahmed and + Collier, Paul and Lin, Susan and Schlusche, Anna Katharina and + Marrocco, Jordan and Williams, Stephen R and Haase, Bettina and + Hayes, Ashley and Chew, Jennifer G and Weisenfeld, Neil I and + Wong, Man Ying and Stein, Alexander N and Hardwick, Simon A and + Hunt, Toby and Wang, Qi and Dieterich, Christoph and Bent, + Zachary and Fedrigo, Olivier and Sloan, Steven A and Risso, + Davide and Jarvis, Erich D and Flicek, Paul and Luo, Wenjie and + Pitt, Geoffrey S and Frankish, Adam and Smit, August B and Ross, + M Elizabeth and Tilgner, Hagen U", + abstract = "Splicing varies across brain regions, but the single-cell + resolution of regional variation is unclear. We present a + single-cell investigation of differential isoform expression + (DIE) between brain regions using single-cell long-read + sequencing in mouse hippocampus and prefrontal cortex in 45 cell + types at postnatal day 7 ( www.isoformAtlas.com ). Isoform tests + for DIE show better performance than exon tests. We detect + hundreds of DIE events traceable to cell types, often + corresponding to functionally distinct protein isoforms. Mostly, + one cell type is responsible for brain-region specific DIE. + However, for fewer genes, multiple cell types influence DIE. + Thus, regional identity can, although rarely, override cell-type + specificity. Cell types indigenous to one anatomic structure + display distinctive DIE, e.g. the choroid plexus epithelium + manifests distinct transcription-start-site usage. Spatial + transcriptomics and long-read sequencing yield a spatially + resolved splicing map. Our methods quantify isoform expression + with cell-type and spatial resolution and it contributes to + further our understanding of how the brain integrates molecular + and cellular complexity.", + journal = "Nat. Commun.", + publisher = "Springer Science and Business Media LLC", + volume = 12, + number = 1, + pages = "463", + month = jan, + year = 2021, + copyright = "https://creativecommons.org/licenses/by/4.0", + language = "en" +} + +@ARTICLE{Mikheenko2022-ql, + title = "Sequencing of individual barcoded {cDNAs} using Pacific + Biosciences and Oxford Nanopore Technologies reveals + platform-specific error patterns", + author = "Mikheenko, Alla and Prjibelski, Andrey D and Joglekar, Anoushka + and Tilgner, Hagen U", + abstract = "Long-read transcriptomics require understanding error sources + inherent to technologies. Current approaches cannot compare + methods for an individual RNA molecule. Here, we present a novel + platform-comparison method that combines barcoding strategies + and long-read sequencing to sequence cDNA copies representing an + individual RNA molecule on both Pacific Biosciences (PacBio) and + Oxford Nanopore Technologies (ONT). We compare these long-read + pairs in terms of sequence content and isoform patterns. + Although individual read pairs show high similarity, we find + differences in (1) aligned length, (2) transcription start site + (TSS), (3) polyadenylation site (poly(A)-site) assignment, and + (4) exon-intron structures. Overall, 25\% of read pairs disagree + on either TSS, poly(A)-site, or splice site. Intron-chain + disagreement typically arises from alignment errors of + microexons and complicated splice sites. Our single-molecule + technology comparison reveals that inconsistencies are often + caused by sequencing error-induced inaccurate ONT alignments, + especially to downstream GUNNGU donor motifs. However, + annotation-disagreeing upstream shifts in NAGNAG acceptors in + ONT are often confirmed by PacBio and are thus likely real. In + both barcoded and nonbarcoded ONT reads, we find that intron + number and proximity of GU/AGs better predict inconsistencies + with the annotation than read quality alone. We summarize these + findings in an annotation-based algorithm for spliced alignment + correction that improves subsequent transcript construction with + ONT reads.", + journal = "Genome Res.", + publisher = "Cold Spring Harbor Laboratory", + volume = 32, + number = 4, + pages = "726--737", + month = apr, + year = 2022, + language = "en" +} + +@ARTICLE{Stein2022-ia, + title = "{ScisorWiz}: visualizing differential isoform expression in + single-cell long-read data", + author = "Stein, Alexander N and Joglekar, Anoushka and Poon, Chi-Lam and + Tilgner, Hagen U", + abstract = "SUMMARY: RNA isoforms contribute to the diverse functionality of + the proteins they encode within the cell. Visualizing how + isoform expression differs across cell types and brain regions + can inform our understanding of disease and gain or loss of + functionality caused by alternative splicing with potential + negative impacts. However, the extent to which this occurs in + specific cell types and brain regions is largely unknown. This + is the kind of information that ScisorWiz plots can provide in + an informative and easily communicable manner. ScisorWiz affords + its user the opportunity to visualize specific genes across any + number of cell types, and provides various sorting options for + the user to gain different ways to understand their data. + ScisorWiz provides a clear picture of differential isoform + expression through various clustering methods and highlights + features such as alternative exons and single-nucleotide + variants. Tools like ScisorWiz are key for interpreting + single-cell isoform sequencing data. This tool applies to any + single-cell long-read RNA sequencing data in any cell type, + tissue or species. AVAILABILITY AND IMPLEMENTATION: Source code + is available at http://github.com/ans4013/ScisorWiz. No new data + were generated for this publication. Data used to generate + figures was sourced from GEO accession token GSE158450 and + available on GitHub as example data.", + journal = "Bioinformatics", + publisher = "Oxford University Press (OUP)", + volume = 38, + number = 13, + pages = "3474--3476", + month = jun, + year = 2022, + keywords = "Computational Neuroscience; Differential Isoform Expression; + Genetics; RNA Splicing", + copyright = "https://creativecommons.org/licenses/by/4.0/", + language = "en" +} + +@ARTICLE{Prjibelski2023-dl, + title = "Accurate isoform discovery with {IsoQuant} using long reads", + author = "Prjibelski, Andrey D and Mikheenko, Alla and Joglekar, Anoushka + and Smetanin, Alexander and Jarroux, Julien and Lapidus, Alla L + and Tilgner, Hagen U", + abstract = "Annotating newly sequenced genomes and determining alternative + isoforms from long-read RNA data are complex and incompletely + solved problems. Here we present IsoQuant-a computational tool + using intron graphs that accurately reconstructs transcripts + both with and without reference genome annotation. For novel + transcript discovery, IsoQuant reduces the false-positive rate + fivefold and 2.5-fold for Oxford Nanopore reference-based or + reference-free mode, respectively. IsoQuant also improves + performance for Pacific Biosciences data.", + journal = "Nat. Biotechnol.", + publisher = "Springer Science and Business Media LLC", + volume = 41, + number = 7, + pages = "915--918", + month = jul, + year = 2023, + copyright = "https://creativecommons.org/licenses/by/4.0", + language = "en" +} + +@ARTICLE{Bashkirova2023-mr, + title = "Opposing, spatially-determined epigenetic forces impose + restrictions on stochastic olfactory receptor choice", + author = "Bashkirova, Elizaveta V and Klimpert, Nell and Monahan, Kevin and + Campbell, Christine E and Osinski, Jason M and Tan, Longzhi and + Schieren, Ira and Pourmorady, Ariel and Stecky, Beka and Barnea, + Gilad and Xie, X Sunnie and Abdus-Saboor, Ishmail and Shykind, + Benjamin and Jones-Marlin, Bianca and Gronostajski, Richard M and + Fleischmann, Alexander and Lomvardas, Stavros", + abstract = "Olfactory receptor (OR) choice represents an example of + genetically hardwired stochasticity, where every olfactory neuron + expresses one out of ~2000 OR alleles in a probabilistic, yet + stereotypic fashion. Here, we propose that topographic + restrictions in OR expression are established in neuronal + progenitors by two opposing forces: polygenic transcription and + genomic silencing, both of which are influenced by dorsoventral + gradients of transcription factors NFIA, B, and X. Polygenic + transcription of OR genes may define spatially constrained OR + repertoires, among which one OR allele is selected for singular + expression later in development. Heterochromatin assembly and + genomic compartmentalization of OR alleles also vary across the + axes of the olfactory epithelium and may preferentially eliminate + ectopically expressed ORs with more dorsal expression + destinations from this ``privileged'' repertoire. Our experiments + identify early transcription as a potential ``epigenetic'' + contributor to future developmental patterning and reveal how two + spatially responsive probabilistic processes may act in concert + to establish deterministic, precise, and reproducible territories + of stochastic gene expression.", + journal = "bioRxivorg", + month = sep, + year = 2023, + language = "en" +} + +@ARTICLE{Sanchez-Ferras2021-yo, + title = "A coordinated progression of progenitor cell states initiates + urinary tract development", + author = "Sanchez-Ferras, Oraly and Pacis, Alain and Sotiropoulou, Maria + and Zhang, Yuhong and Wang, Yu Chang and Bourgey, Mathieu and + Bourque, Guillaume and Ragoussis, Jiannis and Bouchard, Maxime", + abstract = "The kidney and upper urinary tract develop through reciprocal + interactions between the ureteric bud and the surrounding + mesenchyme. Ureteric bud branching forms the arborized + collecting duct system of the kidney, while ureteric tips + promote nephron formation from dedicated progenitor cells. While + nephron progenitor cells are relatively well characterized, the + origin of ureteric bud progenitors has received little attention + so far. It is well established that the ureteric bud is induced + from the nephric duct, an epithelial duct derived from the + intermediate mesoderm of the embryo. However, the cell state + transitions underlying the progression from intermediate + mesoderm to nephric duct and ureteric bud remain unknown. Here + we show that nephric duct morphogenesis results from the + coordinated organization of four major progenitor cell + populations. Using single cell RNA-seq and Cluster RNA-seq, we + show that these progenitors emerge in time and space according + to a stereotypical pattern. We identify the transcription + factors Tfap2a/b and Gata3 as critical coordinators of this + progenitor cell progression. This study provides a better + understanding of the cellular origin of the renal collecting + duct system and associated urinary tract developmental diseases, + which may inform guided differentiation of functional kidney + tissue.", + journal = "Nat. Commun.", + publisher = "Springer Science and Business Media LLC", + volume = 12, + number = 1, + pages = "2627", + month = may, + year = 2021, + copyright = "https://creativecommons.org/licenses/by/4.0", + language = "en" +} + +@ARTICLE{Parigi2022-mo, + title = "The spatial transcriptomic landscape of the healing mouse + intestine following damage", + author = "Parigi, Sara M and Larsson, Ludvig and Das, Srustidhar and + Ramirez Flores, Ricardo O and Frede, Annika and Tripathi, Kumar + P and Diaz, Oscar E and Selin, Katja and Morales, Rodrigo A and + Luo, Xinxin and Monasterio, Gustavo and Engblom, Camilla and + Gagliani, Nicola and Saez-Rodriguez, Julio and Lundeberg, Joakim + and Villablanca, Eduardo J", + abstract = "The intestinal barrier is composed of a complex cell network + defining highly compartmentalized and specialized structures. + Here, we use spatial transcriptomics to define how the + transcriptomic landscape is spatially organized in the steady + state and healing murine colon. At steady state conditions, we + demonstrate a previously unappreciated molecular regionalization + of the colon, which dramatically changes during mucosal healing. + Here, we identified spatially-organized transcriptional programs + defining compartmentalized mucosal healing, and regions with + dominant wired pathways. Furthermore, we showed that decreased + p53 activation defined areas with increased presence of + proliferating epithelial stem cells. Finally, we mapped + transcriptomics modules associated with human diseases + demonstrating the translational potential of our dataset. + Overall, we provide a publicly available resource defining + principles of transcriptomic regionalization of the colon during + mucosal healing and a framework to develop and progress further + hypotheses.", + journal = "Nat. Commun.", + publisher = "Springer Science and Business Media LLC", + volume = 13, + number = 1, + pages = "828", + month = feb, + year = 2022, + copyright = "https://creativecommons.org/licenses/by/4.0", + language = "en" +} + +@ARTICLE{Tower2021-yy, + title = "Spatial transcriptomics reveals a role for sensory nerves in + preserving cranial suture patency through modulation of + {BMP/TGF-$\beta$} signaling", + author = "Tower, Robert J and Li, Zhu and Cheng, Yu-Hao and Wang, Xue-Wei + and Rajbhandari, Labchan and Zhang, Qian and Negri, Stefano and + Uytingco, Cedric R and Venkatesan, Arun and Zhou, Feng-Quan and + Cahan, Patrick and James, Aaron W and Clemens, Thomas L", + abstract = "The patterning and ossification of the mammalian skeleton + requires the coordinated actions of both intrinsic bone + morphogens and extrinsic neurovascular signals, which function + in a temporal and spatial fashion to control mesenchymal + progenitor cell (MPC) fate. Here, we show the genetic inhibition + of tropomyosin receptor kinase A (TrkA) sensory nerve + innervation of the developing cranium results in premature + calvarial suture closure, associated with a decrease in suture + MPC proliferation and increased mineralization. In vitro, axons + from peripheral afferent neurons derived from dorsal root + ganglions (DRGs) of wild-type mice induce MPC proliferation in a + spatially restricted manner via a soluble factor when cocultured + in microfluidic chambers. Comparative spatial transcriptomic + analysis of the cranial sutures in vivo confirmed a positive + association between sensory axons and proliferative MPCs. + SpatialTime analysis across the developing suture revealed + regional-specific alterations in bone morphogenetic protein + (BMP) and TGF-$\beta$ signaling pathway transcripts in response + to TrkA inhibition. RNA sequencing of DRG cell bodies, following + direct, axonal coculture with MPCs, confirmed the alterations in + BMP/TGF-$\beta$ signaling pathway transcripts. Among these, the + BMP inhibitor follistatin-like 1 (FSTL1) replicated key features + of the neural-to-bone influence, including mitogenic and + anti-osteogenic effects via the inhibition of BMP/TGF-$\beta$ + signaling. Taken together, our results demonstrate that sensory + nerve-derived signals, including FSTL1, function to coordinate + cranial bone patterning by regulating MPC proliferation and + differentiation in the suture mesenchyme.", + journal = "Proc. Natl. Acad. Sci. U. S. A.", + publisher = "Proceedings of the National Academy of Sciences", + volume = 118, + number = 42, + pages = "e2103087118", + month = oct, + year = 2021, + keywords = "TrkA; calvarial bone; cranial suture; skeletal innervation; + spatial transcriptomics", + copyright = "https://www.pnas.org/site/aboutpnas/licenses.xhtml", + language = "en" +} + +@ARTICLE{Meylan2022-wt, + title = "Tertiary lymphoid structures generate and propagate anti-tumor + antibody-producing plasma cells in renal cell cancer", + author = "Meylan, Maxime and Petitprez, Florent and Becht, Etienne and + Bougo{\"u}in, Antoine and Pupier, Guilhem and Calvez, Anne and + Giglioli, Ilenia and Verkarre, Virginie and Lacroix, Guillaume + and Verneau, Johanna and Sun, Chen-Ming and Laurent-Puig, Pierre + and Vano, Yann-Alexandre and Ela{\"\i}di, Reza and M{\'e}jean, + Arnaud and Sanchez-Salas, Rafa{\"e}l and Barret, Eric and + Cathelineau, Xavier and Oudard, Stephane and Reynaud, + Claude-Agn{\`e}s and de Reyni{\`e}s, Aur{\'e}lien and + Saut{\`e}s-Fridman, Catherine and Fridman, Wolf Herman", + abstract = "The presence of intratumoral tertiary lymphoid structures (TLS) + is associated with positive clinical outcomes and responses to + immunotherapy in cancer. Here, we used spatial transcriptomics + to examine the nature of B cell responses within TLS in renal + cell carcinoma (RCC). B cells were enriched in TLS, and therein, + we could identify all B cell maturation stages toward plasma + cell (PC) formation. B cell repertoire analysis revealed clonal + diversification, selection, expansion in TLS, and the presence + of fully mature clonotypes at distance. In TLS+ tumors, IgG- and + IgA-producing PCs disseminated into the tumor beds along + fibroblastic tracks. TLS+ tumors exhibited high frequencies of + IgG-producing PCs and IgG-stained and apoptotic malignant cells, + suggestive of anti-tumor effector activity. Therapeutic + responses and progression-free survival correlated with + IgG-stained tumor cells in RCC patients treated with immune + checkpoint inhibitors. Thus, intratumoral TLS sustains B cell + maturation and antibody production that is associated with + response to immunotherapy, potentially via direct anti-tumor + effects.", + journal = "Immunity", + publisher = "Elsevier BV", + volume = 55, + number = 3, + pages = "527--541.e5", + month = mar, + year = 2022, + keywords = "B cell maturation; B cell repertoire; Visium; anti-tumor IgG; + fibroblasts; plasma cells; renal cell cancer; response to immune + check point inhibition; spatial transcriptomics; tertiary + lymphoid structures; tumor microenvironment", + copyright = "http://www.elsevier.com/open-access/userlicense/1.0/", + language = "en" +} + +@ARTICLE{Ni2022-ap, + title = "{SpotClean} adjusts for spot swapping in spatial transcriptomics + data", + author = "Ni, Zijian and Prasad, Aman and Chen, Shuyang and Halberg, + Richard B and Arkin, Lisa M and Drolet, Beth A and Newton, + Michael A and Kendziorski, Christina", + abstract = "Spatial transcriptomics is a powerful and widely used approach + for profiling the gene expression landscape across a tissue with + emerging applications in molecular medicine and tumor + diagnostics. Recent spatial transcriptomics experiments utilize + slides containing thousands of spots with spot-specific barcodes + that bind RNA. Ideally, unique molecular identifiers (UMIs) at a + spot measure spot-specific expression, but this is often not the + case in practice due to bleed from nearby spots, an artifact we + refer to as spot swapping. To improve the power and precision of + downstream analyses in spatial transcriptomics experiments, we + propose SpotClean, a probabilistic model that adjusts for spot + swapping to provide more accurate estimates of gene-specific UMI + counts. SpotClean provides substantial improvements in marker + gene analyses and in clustering, especially when tissue regions + are not easily separated. As demonstrated in multiple studies of + cancer, SpotClean improves tumor versus normal tissue + delineation and improves tumor burden estimation thus increasing + the potential for clinical and diagnostic applications of + spatial transcriptomics technologies.", + journal = "Nat. Commun.", + publisher = "Springer Science and Business Media LLC", + volume = 13, + number = 1, + pages = "2971", + month = may, + year = 2022, + copyright = "https://creativecommons.org/licenses/by/4.0", + language = "en" +} + +@ARTICLE{Kadur_Lakshminarasimha_Murthy2022-ch, + title = "Human distal lung maps and lineage hierarchies reveal a bipotent + progenitor", + author = "Kadur Lakshminarasimha Murthy, Preetish and Sontake, Vishwaraj + and Tata, Aleksandra and Kobayashi, Yoshihiko and Macadlo, + Lauren and Okuda, Kenichi and Conchola, Ansley S and Nakano, + Satoko and Gregory, Simon and Miller, Lisa A and Spence, Jason R + and Engelhardt, John F and Boucher, Richard C and Rock, Jason R + and Randell, Scott H and Tata, Purushothama Rao", + abstract = "Mapping the spatial distribution and molecular identity of + constituent cells is essential for understanding tissue dynamics + in health and disease. We lack a comprehensive map of human + distal airways, including the terminal and respiratory + bronchioles (TRBs), which are implicated in respiratory + diseases1-4. Here, using spatial transcriptomics and single-cell + profiling of microdissected distal airways, we identify + molecularly distinct TRB cell types that have not-to our + knowledge-been previously characterized. These include + airway-associated LGR5+ fibroblasts and TRB-specific alveolar + type-0 (AT0) cells and TRB secretory cells (TRB-SCs). Connectome + maps and organoid-based co-cultures reveal that LGR5+ + fibroblasts form a signalling hub in the airway niche. AT0 cells + and TRB-SCs are conserved in primates and emerge dynamically + during human lung development. Using a non-human primate model + of lung injury, together with human organoids and tissue + specimens, we show that alveolar type-2 cells in regenerating + lungs transiently acquire an AT0 state from which they can + differentiate into either alveolar type-1 cells or TRB-SCs. This + differentiation programme is distinct from that identified in + the mouse lung5-7. Our study also reveals mechanisms that drive + the differentiation of the bipotent AT0 cell state into normal + or pathological states. In sum, our findings revise human lung + cell maps and lineage trajectories, and implicate an epithelial + transitional state in primate lung regeneration and disease.", + journal = "Nature", + publisher = "Springer Science and Business Media LLC", + volume = 604, + number = 7904, + pages = "111--119", + month = apr, + year = 2022, + language = "en" +} + +@ARTICLE{Foster2021-br, + title = "Integrated spatial multiomics reveals fibroblast fate during + tissue repair", + author = "Foster, Deshka S and Januszyk, Michael and Yost, Kathryn E and + Chinta, Malini S and Gulati, Gunsagar S and Nguyen, Alan T and + Burcham, Austin R and Salhotra, Ankit and Ransom, R Chase and + Henn, Dominic and Chen, Kellen and Mascharak, Shamik and + Tolentino, Karen and Titan, Ashley L and Jones, R Ellen and da + Silva, Oscar and Leavitt, W Tripp and Marshall, Clement D and + des Jardins-Park, Heather E and Hu, Michael S and Wan, Derrick C + and Wernig, Gerlinde and Wagh, Dhananjay and Coller, John and + Norton, Jeffrey A and Gurtner, Geoffrey C and Newman, Aaron M + and Chang, Howard Y and Longaker, Michael T", + abstract = "In the skin, tissue injury results in fibrosis in the form of + scars composed of dense extracellular matrix deposited by + fibroblasts. The therapeutic goal of regenerative wound healing + has remained elusive, in part because principles of fibroblast + programming and adaptive response to injury remain incompletely + understood. Here, we present a multimodal -omics platform for + the comprehensive study of cell populations in complex tissue, + which has allowed us to characterize the cells involved in wound + healing across both time and space. We employ a stented wound + model that recapitulates human tissue repair kinetics and + multiple Rainbow transgenic lines to precisely track fibroblast + fate during the physiologic response to skin injury. Through + integrated analysis of single cell chromatin landscapes and gene + expression states, coupled with spatial transcriptomic + profiling, we are able to impute fibroblast epigenomes with + temporospatial resolution. This has allowed us to reveal + potential mechanisms controlling fibroblast fate during + migration, proliferation, and differentiation following skin + injury, and thereby reexamine the canonical phases of wound + healing. These findings have broad implications for the study of + tissue repair in complex organ systems.", + journal = "Proc. Natl. Acad. Sci. U. S. A.", + publisher = "Proceedings of the National Academy of Sciences", + volume = 118, + number = 41, + pages = "e2110025118", + month = oct, + year = 2021, + keywords = "chromatin accessibility; fibrosis; multiomics; spatial + epigenomics; spatial transcriptomics", + copyright = "https://creativecommons.org/licenses/by/4.0/", + language = "en" +} + +@ARTICLE{Sudmeier2022-nf, + title = "Distinct phenotypic states and spatial distribution of {CD8+} + {T} cell clonotypes in human brain metastases", + author = "Sudmeier, Lisa J and Hoang, Kimberly B and Nduom, Edjah K and + Wieland, Andreas and Neill, Stewart G and Schniederjan, Matthew + J and Ramalingam, Suresh S and Olson, Jeffrey J and Ahmed, Rafi + and Hudson, William H", + abstract = "Metastatic disease in the brain is difficult to control and + predicts poor prognosis. Here, we analyze human brain metastases + and demonstrate their robust infiltration by CD8+ T cell subsets + with distinct antigen specificities, phenotypic states, and + spatial localization within the tumor microenvironment. Brain + metastases are densely infiltrated by T cells; the majority of + infiltrating CD8+ T cells express PD-1. Single-cell RNA + sequencing shows significant clonal overlap between + proliferating and exhausted CD8+ T cells, but these subsets have + minimal clonal overlap with circulating and other + tumor-infiltrating CD8+ T cells, including bystander CD8+ T + cells specific for microbial antigens. Using spatial + transcriptomics and spatial T cell receptor (TCR) sequencing, we + show these clonally unrelated, phenotypically distinct CD8+ T + cell populations occupy discrete niches within the brain + metastasis tumor microenvironment. Together, our work identifies + signaling pathways within CD8+ T cells and in their surrounding + environment that may be targeted for immunotherapy of brain + metastases.", + journal = "Cell Rep. Med.", + publisher = "Elsevier BV", + volume = 3, + number = 5, + pages = "100620", + month = may, + year = 2022, + keywords = "CD8(+) T cells; TCR-sequencing; brain metastases; bystander; + exhaustion; spatial transcriptomics", + copyright = "http://creativecommons.org/licenses/by/4.0/", + language = "en" +} + +@ARTICLE{Hudson2022-mz, + title = "Localization of {T} cell clonotypes using the Visium spatial + transcriptomics platform", + author = "Hudson, William H and Sudmeier, Lisa J", + abstract = "We present a protocol to localize T cell receptor clones using + the Visium spatial transcriptomics platform. This approach + permits simultaneous localization of both gene expression and T + cell clonotypes in situ within tissue sections. T cell receptor + sequences identified by this protocol are readily recapitulated + by single-cell sequencing. This technique enables detailed + studies of the spatial organization of the human T cell + repertoire, such as the localization of infiltrating T cell + clones within the tumor microenvironment. For complete details + on the use and execution of this protocol, please refer to + Sudmeier et al. (2022).", + journal = "STAR Protoc.", + publisher = "Elsevier BV", + volume = 3, + number = 2, + pages = "101391", + month = jun, + year = 2022, + keywords = "Immunology; Molecular Biology; Sequence analysis", + copyright = "http://creativecommons.org/licenses/by/4.0/", + language = "en" +} + +@ARTICLE{Tower2022-fi, + title = "Spatial transcriptomics reveals metabolic changes underly + age-dependent declines in digit regeneration", + author = "Tower, Robert J and Busse, Emily and Jaramillo, Josue and Lacey, + Michelle and Hoffseth, Kevin and Guntur, Anyonya R and Simkin, + Jennifer and Sammarco, Mimi C", + abstract = "De novo limb regeneration after amputation is restricted in + mammals to the distal digit tip. Central to this regenerative + process is the blastema, a heterogeneous population of + lineage-restricted, dedifferentiated cells that ultimately + orchestrates regeneration of the amputated bone and surrounding + soft tissue. To investigate skeletal regeneration, we made use + of spatial transcriptomics to characterize the transcriptional + profile specifically within the blastema. Using this technique, + we generated a gene signature with high specificity for the + blastema in both our spatial data, as well as other previously + published single-cell RNA-sequencing transcriptomic studies. To + elucidate potential mechanisms distinguishing regenerative from + non-regenerative healing, we applied spatial transcriptomics to + an aging model. Consistent with other forms of repair, our digit + amputation mouse model showed a significant impairment in + regeneration in aged mice. Contrasting young and aged mice, + spatial analysis revealed a metabolic shift in aged blastema + associated with an increased bioenergetic requirement. This + enhanced metabolic turnover was associated with increased + hypoxia and angiogenic signaling, leading to excessive + vascularization and altered regenerated bone architecture in + aged mice. Administration of the metabolite oxaloacetate + decreased the oxygen consumption rate of the aged blastema and + increased WNT signaling, leading to enhanced in vivo bone + regeneration. Thus, targeting cell metabolism may be a promising + strategy to mitigate aging-induced declines in tissue + regeneration.", + journal = "Elife", + publisher = "eLife Sciences Publications, Ltd", + volume = 11, + month = may, + year = 2022, + keywords = "aging; bone regeneration; cell biology; cell metabolism; digit + regeneration; mouse; oxaloacetate; spatial transcriptomics", + copyright = "http://creativecommons.org/licenses/by/4.0/", + language = "en" +} + +@ARTICLE{Rustagi2022-io, + title = "Endothelial phospholipase {C$\gamma$2} improves outcomes of + diabetic ischemic limb rescue following {VEGF} therapy", + author = "Rustagi, Yashika and Abouhashem, Ahmed S and Verma, Priyanka and + Verma, Sumit S and Hernandez, Edward and Liu, Sheng and Kumar, + Manishekhar and Guda, Poornachander R and Srivastava, Rajneesh + and Mohanty, Sujit K and Kacar, Sedat and Mahajan, Sanskruti and + Wanczyk, Kristen E and Khanna, Savita and Murphy, Michael P and + Gordillo, Gayle M and Roy, Sashwati and Wan, Jun and Sen, + Chandan K and Singh, Kanhaiya", + abstract = "Therapeutic vascular endothelial growth factor (VEGF) + replenishment has met with limited success for the management of + critical limb-threatening ischemia. To improve outcomes of VEGF + therapy, we applied single-cell RNA sequencing (scRNA-seq) + technology to study the endothelial cells of the human diabetic + skin. Single-cell suspensions were generated from the human skin + followed by cDNA preparation using the Chromium Next GEM + Single-cell 3' Kit v3.1. Using appropriate quality control + measures, 36,487 cells were chosen for downstream analysis. + scRNA-seq studies identified that although VEGF signaling was + not significantly altered in diabetic versus nondiabetic skin, + phospholipase C$\gamma$2 (PLC$\gamma$2) was downregulated. The + significance of PLC$\gamma$2 in VEGF-mediated increase in + endothelial cell metabolism and function was assessed in + cultured human microvascular endothelial cells. In these cells, + VEGF enhanced mitochondrial function, as indicated by elevation + in oxygen consumption rate and extracellular acidification rate. + The VEGF-dependent increase in cell metabolism was blunted in + response to PLC$\gamma$2 inhibition. Follow-up rescue studies + therefore focused on understanding the significance of VEGF + therapy in presence or absence of endothelial PLC$\gamma$2 in + type 1 (streptozotocin-injected) and type 2 (db/db) diabetic + ischemic tissue. Nonviral topical tissue nanotransfection + technology (TNT) delivery of CDH5 promoter-driven PLC$\gamma$2 + open reading frame promoted the rescue of hindlimb ischemia in + diabetic mice. Improvement of blood flow was also associated + with higher abundance of VWF+/CD31+ and VWF+/SMA+ + immunohistochemical staining. TNT-based gene delivery was not + associated with tissue edema, a commonly noted complication + associated with proangiogenic gene therapies. Taken together, + our study demonstrates that TNT-mediated delivery of endothelial + PLC$\gamma$2, as part of combination gene therapy, is effective + in diabetic ischemic limb rescue.", + journal = "Diabetes", + publisher = "American Diabetes Association", + volume = 71, + number = 5, + pages = "1149--1165", + month = may, + year = 2022, + copyright = "https://www.diabetesjournals.org/journals/pages/license", + language = "en" +} + +@ARTICLE{Dixon2022-ew, + title = "Spatially resolved transcriptomic analysis of acute kidney + injury in a female Murine model", + author = "Dixon, Eryn E and Wu, Haojia and Muto, Yoshiharu and Wilson, + Parker C and Humphreys, Benjamin D", + abstract = "BACKGROUND: Single-cell sequencing technologies have advanced + our understanding of kidney biology and disease, but the loss of + spatial information in these datasets hinders our interpretation + of intercellular communication networks and regional gene + expression patterns. New spatial transcriptomic sequencing + platforms make it possible to measure the topography of gene + expression at genome depth. METHODS: We optimized and validated + a female bilateral ischemia-reperfusion injury model. Using the + 10$\times$ Genomics Visium Spatial Gene Expression solution, we + generated spatial maps of gene expression across the injury and + repair time course, and applied two open-source computational + tools, Giotto and SPOTlight, to increase resolution and measure + cell-cell interaction dynamics. RESULTS: An ischemia time of 34 + minutes in a female murine model resulted in comparable injury + to 22 minutes for males. We report a total of 16,856 unique + genes mapped across our injury and repair time course. Giotto, a + computational toolbox for spatial data analysis, enabled + increased resolution mapping of genes and cell types. Using a + seeded nonnegative matrix regression (SPOTlight) to deconvolute + the dynamic landscape of cell-cell interactions, we found that + injured proximal tubule cells were characterized by increasing + macrophage and lymphocyte interactions even 6 weeks after + injury, potentially reflecting the AKI to CKD transition. + CONCLUSIONS: In this transcriptomic atlas, we defined + region-specific and injury-induced loss of differentiation + markers and their re-expression during repair, as well as + region-specific injury and repair transcriptional responses. + Lastly, we created an interactive data visualization application + for the scientific community to explore these results + (http://humphreyslab.com/SingleCell/).", + journal = "J. Am. Soc. Nephrol.", + publisher = "Ovid Technologies (Wolters Kluwer Health)", + volume = 33, + number = 2, + pages = "279--289", + month = feb, + year = 2022, + keywords = "AKI; spatial; transcriptomics", + language = "en" +} + +@ARTICLE{Lake2023-mf, + title = "An atlas of healthy and injured cell states and niches in the + human kidney", + author = "Lake, Blue B and Menon, Rajasree and Winfree, Seth and Hu, Qiwen + and Melo Ferreira, Ricardo and Kalhor, Kian and Barwinska, Daria + and Otto, Edgar A and Ferkowicz, Michael and Diep, Dinh and + Plongthongkum, Nongluk and Knoten, Amanda and Urata, Sarah and + Mariani, Laura H and Naik, Abhijit S and Eddy, Sean and Zhang, Bo + and Wu, Yan and Salamon, Diane and Williams, James C and Wang, + Xin and Balderrama, Karol S and Hoover, Paul J and Murray, Evan + and Marshall, Jamie L and Noel, Teia and Vijayan, Anitha and + Hartman, Austin and Chen, Fei and Waikar, Sushrut S and Rosas, + Sylvia E and Wilson, Francis P and Palevsky, Paul M and Kiryluk, + Krzysztof and Sedor, John R and Toto, Robert D and Parikh, Chirag + R and Kim, Eric H and Satija, Rahul and Greka, Anna and Macosko, + Evan Z and Kharchenko, Peter V and Gaut, Joseph P and Hodgin, + Jeffrey B and {KPMP Consortium} and Eadon, Michael T and Dagher, + Pierre C and El-Achkar, Tarek M and Zhang, Kun and Kretzler, + Matthias and Jain, Sanjay", + abstract = "Understanding kidney disease relies on defining the complexity of + cell types and states, their associated molecular profiles and + interactions within tissue neighbourhoods1. Here we applied + multiple single-cell and single-nucleus assays (>400,000 nuclei + or cells) and spatial imaging technologies to a broad spectrum of + healthy reference kidneys (45 donors) and diseased kidneys (48 + patients). This has provided a high-resolution cellular atlas of + 51 main cell types, which include rare and previously undescribed + cell populations. The multi-omic approach provides detailed + transcriptomic profiles, regulatory factors and spatial + localizations spanning the entire kidney. We also define 28 + cellular states across nephron segments and interstitium that + were altered in kidney injury, encompassing cycling, adaptive + (successful or maladaptive repair), transitioning and + degenerative states. Molecular signatures permitted the + localization of these states within injury neighbourhoods using + spatial transcriptomics, while large-scale 3D imaging analysis + (around 1.2 million neighbourhoods) provided corresponding + linkages to active immune responses. These analyses defined + biological pathways that are relevant to injury time-course and + niches, including signatures underlying epithelial repair that + predicted maladaptive states associated with a decline in kidney + function. This integrated multimodal spatial cell atlas of + healthy and diseased human kidneys represents a comprehensive + benchmark of cellular states, neighbourhoods, outcome-associated + signatures and publicly available interactive visualizations.", + journal = "Nature", + volume = 619, + number = 7970, + pages = "585--594", + month = jul, + year = 2023, + language = "en" +} + +@ARTICLE{Mohammadi2023-uv, + title = "Size matters: the impact of nucleus size on results from spatial + transcriptomics", + author = "Mohammadi, Elyas and Chojnowska, Katarzyna and Bie{\'n}kowski, + Micha{\l} and Kostecka, Anna and Koczkowska, Magdalena and + {\.Z}mijewski, Micha{\l} A and J{\k a}kalski, Marcin and + Ingelsson, Martin and Filipowicz, Natalia and Olszewski, + Pawe{\l} and Davies, Hanna and Wierzbicka, Justyna M and Hyman, + Bradley T and Dumanski, Jan P and Piotrowski, Arkadiusz and + Mieczkowski, Jakub", + abstract = "BACKGROUND: Visium Spatial Gene Expression (ST) is a method + combining histological spatial information with transcriptomics + profiles directly from tissue sections. The use of spatial + information has made it possible to discover new modes of gene + expression regulations. However, in the ST experiment, the + nucleus size of cells may exceed the thickness of a tissue + slice. This may, in turn, negatively affect comprehensive + capturing the transcriptomics profile in a single slice, + especially for tissues having large differences in the size of + nuclei. METHODS: Here, we defined the effect of Consecutive + Slices Data Integration (CSDI) on unveiling accurate spot + clustering and deconvolution of spatial transcriptomic spots in + human postmortem brains. By considering the histological + information as reference, we assessed the improvement of + unsupervised clustering and single nuclei RNA-seq and ST data + integration before and after CSDI. RESULTS: Apart from the + escalated number of defined clusters representing neuronal + layers, the pattern of clusters in consecutive sections was + concordant only after CSDI. Besides, the assigned cell labels to + spots matches the histological pattern of tissue sections after + CSDI. CONCLUSION: CSDI can be applied to investigate consecutive + sections studied with ST in the human cerebral cortex, avoiding + misinterpretation of spot clustering and annotation, increasing + accuracy of cell recognition as well as improvement in + uncovering the layers of grey matter in the human brain.", + journal = "J. Transl. Med.", + publisher = "Springer Science and Business Media LLC", + volume = 21, + number = 1, + pages = "270", + month = apr, + year = 2023, + keywords = "Cerebral cortex; Consecutive tissue sections; Data integration; + Neuronal nuclei; Spatial transcriptomics", + copyright = "https://creativecommons.org/licenses/by/4.0", + language = "en" +} + +@ARTICLE{Yamasaki2022-bq, + title = "{MEK} inhibition suppresses metastatic progression of + {KRAS-mutated} gastric cancer", + author = "Yamasaki, Juntaro and Hirata, Yuki and Otsuki, Yuji and Suina, + Kentaro and Saito, Yoshiyuki and Masuda, Kenta and Okazaki, + Shogo and Ishimoto, Takatsugu and Saya, Hideyuki and Nagano, + Osamu", + abstract = "Metastatic progression of tumors is driven by genetic + alterations and tumor-stroma interaction. To elucidate the + mechanism underlying the oncogene-induced gastric tumor + progression, we have developed an organoid-based model of + gastric cancer from GAstric Neoplasia (GAN) mice, which express + Wnt1 and the enzymes COX2 and microsomal prostaglandin E + synthase 1 in the stomach. Both p53 knockout (GAN-p53KO) + organoids and KRASG12V -expressing GAN-p53KO (GAN-KP) organoids + were generated by genetic manipulation of GAN mouse-derived + tumor (GAN wild-type [WT]) organoids. In contrast with GAN-WT + and GAN-p53KO organoids, which manifested Wnt addiction, GAN-KP + organoids showed a Wnt-independent phenotype and the ability to + proliferate without formation of a Wnt-regulated + three-dimensional epithelial architecture. After transplantation + in syngeneic mouse stomach, GAN-p53KO cells formed only small + tumors, whereas GAN-KP cells gave rise to invasive tumors + associated with the development of hypoxia as well as to liver + metastasis. Spatial transcriptomics analysis suggested that + hypoxia signaling contributes to the metastatic progression of + GAN-KP tumors. In particular, such analysis identified a cluster + of stromal cells located at the tumor invasive front that + expressed genes related to hypoxia signaling, angiogenesis, and + cell migration. These cells were also positive for + phosphorylated extracellular signal-regulated kinase (ERK), + suggesting that mitogen-activated protein kinase (MAPK) + signaling promotes development of both tumor and + microenvironment. The MEK (MAPK kinase) inhibitor trametinib + suppressed the development of GAN-KP gastric tumors, formation + of a hypoxic microenvironment, tumor angiogenesis, and liver + metastasis. Our findings therefore establish a rationale for + application of trametinib to suppress metastatic progression of + KRAS-mutated gastric cancer.", + journal = "Cancer Sci.", + publisher = "Wiley", + volume = 113, + number = 3, + pages = "916--925", + month = mar, + year = 2022, + keywords = "MEK; epithelial-mesenchymal transition (EMT); gastric cancer; + hypoxia; mouse model", + copyright = "http://creativecommons.org/licenses/by-nc/4.0/", + language = "en" +} + +@ARTICLE{Chen2022-en, + title = "Prostaglandin {E2} synchronizes lunar-regulated beach spawning + in grass puffers", + author = "Chen, Junfeng and Katada, Yuma and Okimura, Kousuke and + Yamaguchi, Taiki and Guh, Ying-Jey and Nakayama, Tomoya and + Maruyama, Michiyo and Furukawa, Yuko and Nakane, Yusuke and + Yamamoto, Naoyuki and Sato, Yoshikatsu and Ando, Hironori and + Sugimura, Asako and Tabata, Kazufumi and Sato, Ayato and + Yoshimura, Takashi", + abstract = "Many organisms living along the coastlines synchronize their + reproduction with the lunar cycle. At the time of spring tide, + thousands of grass puffers (Takifugu alboplumbeus) aggregate and + vigorously tremble their bodies at the water's edge to spawn. To + understand the mechanisms underlying this spectacular semilunar + beach spawning, we collected the hypothalamus and pituitary from + male grass puffers every week for 2 months. RNA sequencing + (RNA-seq) analysis identified 125 semilunar genes, including + genes crucial for reproduction (e.g., gonadotropin-releasing + hormone 1 [gnrh1], luteinizing hormone $\beta$ subunit [lhb]) + and receptors for pheromone prostaglandin E (PGE). PGE2 is + secreted into the seawater during the spawning, and its + administration activates olfactory sensory neurons and triggers + trembling behavior of surrounding individuals. These results + suggest that PGE2 synchronizes lunar-regulated beach-spawning + behavior in grass puffers. To further explore the mechanism that + regulates the lunar-synchronized transcription of semilunar + genes, we searched for semilunar transcription factors. Spatial + transcriptomics and multiplex fluorescent in situ hybridization + showed co-localization of the semilunar transcription factor + CCAAT/enhancer-binding protein $\delta$ (cebpd) and gnrh1, and + cebpd induced the promoter activity of gnrh1. Taken together, + our study demonstrates semilunar genes that mediate + lunar-synchronized beach-spawning behavior. VIDEO ABSTRACT.", + journal = "Curr. Biol.", + publisher = "Elsevier BV", + volume = 32, + number = 22, + pages = "4881--4889.e5", + month = nov, + year = 2022, + keywords = "beach spawning; biological clock; circalunar rhythms; grass + puffer; lunar cycle; neap tide; pheromone; seasonal + reproduction; semilunar rhythm; spring tide", + language = "en" +} + +@ARTICLE{Russ2022-sy, + title = "Spatially resolved transcriptomic profiling of ovarian aging in + mice", + author = "Russ, Jennifer E and Haywood, Mary E and Lane, Sydney L and + Schoolcraft, William B and Katz-Jaffe, Mandy G", + abstract = "Ovarian aging precedes that of any other mammalian organ and is + the primary cause of female age-related infertility. The + biological mechanisms responsible for ovarian aging remain + unclear. Previous studies have been limited by their use of bulk + RNA-sequencing, which masks the dynamic and heterogeneous nature + of the ovary. In this study, we spatially resolved the + transcriptomic landscape of ovaries from young and aged outbred + mice. In total, we defined eight main ovarian cell populations, + all of which were characterized by significant transcriptomic + changes between young and aged samples. Further sub-cluster + analysis revealed separate transcriptomes for distinct granulosa + cell populations found in young versus aged mice, in addition to + an oocyte sub-cluster population completely absent from aged + mouse ovaries. This study provides a new perspective on + mammalian ovarian aging using spatial transcriptomics to achieve + deeper understanding of the localization and + cell-population-specific mechanisms underlying age-related + fertility decline.", + journal = "iScience", + publisher = "Elsevier BV", + volume = 25, + number = 8, + pages = "104819", + month = aug, + year = 2022, + keywords = "Cellular physiology; Omics; Physiology; Transcriptomics", + copyright = "http://creativecommons.org/licenses/by-nc-nd/4.0/", + language = "en" +} + +@ARTICLE{Misra2021-pr, + title = "Characterizing neonatal heart maturation, regeneration, and scar + resolution using spatial transcriptomics", + author = "Misra, Adwiteeya and Baker, Cameron D and Pritchett, Elizabeth M + and Burgos Villar, Kimberly N and Ashton, John M and Small, Eric + M", + abstract = "The neonatal mammalian heart exhibits a remarkable regenerative + potential, which includes fibrotic scar resolution and the + generation of new cardiomyocytes. To investigate the mechanisms + facilitating heart repair after apical resection in neonatal + mice, we conducted bulk and spatial transcriptomic analyses at + regenerative and non-regenerative timepoints. Importantly, + spatial transcriptomics provided near single-cell resolution, + revealing distinct domains of atrial and ventricular myocardium + that exhibit dynamic phenotypic alterations during postnatal + heart maturation. Spatial transcriptomics also defined the + cardiac scar, which transitions from a proliferative to + secretory phenotype as the heart loses regenerative potential. + The resolving scar is characterized by spatially and temporally + restricted programs of inflammation, epicardium expansion and + extracellular matrix production, metabolic reprogramming, + lipogenic scar extrusion, and cardiomyocyte restoration. + Finally, this study revealed the emergence of a regenerative + border zone defined by immature cardiomyocyte markers and the + robust expression of Sprr1a. Taken together, our study defines + the spatially and temporally restricted gene programs that + underlie neonatal heart regeneration and provides insight into + cardio-restorative mechanisms supporting scar resolution.", + journal = "J. Cardiovasc. Dev. Dis.", + publisher = "MDPI AG", + volume = 9, + number = 1, + pages = "1", + month = dec, + year = 2021, + keywords = "fibroblast; heart; mouse; regeneration; scar; spatial + transcriptomics", + copyright = "https://creativecommons.org/licenses/by/4.0/", + language = "en" +} + +@ARTICLE{Guilliams2022-kd, + title = "Spatial proteogenomics reveals distinct and evolutionarily + conserved hepatic macrophage niches", + author = "Guilliams, Martin and Bonnardel, Johnny and Haest, Birthe and + Vanderborght, Bart and Wagner, Camille and Remmerie, Anneleen + and Bujko, Anna and Martens, Liesbet and Thon{\'e}, Tinne and + Browaeys, Robin and De Ponti, Federico F and Vanneste, Bavo and + Zwicker, Christian and Svedberg, Freya R and Vanhalewyn, Tineke + and Gon{\c c}alves, Amanda and Lippens, Saskia and Devriendt, + Bert and Cox, Eric and Ferrero, Giuliano and Wittamer, Valerie + and Willaert, Andy and Kaptein, Suzanne J F and Neyts, Johan and + Dallmeier, Kai and Geldhof, Peter and Casaert, Stijn and + Deplancke, Bart and Ten Dijke, Peter and Hoorens, Anne and + Vanlander, Aude and Berrevoet, Frederik and Van Nieuwenhove, + Yves and Saeys, Yvan and Saelens, Wouter and Van Vlierberghe, + Hans and Devisscher, Lindsey and Scott, Charlotte L", + abstract = "The liver is the largest solid organ in the body, yet it remains + incompletely characterized. Here we present a spatial + proteogenomic atlas of the healthy and obese human and murine + liver combining single-cell CITE-seq, single-nuclei sequencing, + spatial transcriptomics, and spatial proteomics. By integrating + these multi-omic datasets, we provide validated strategies to + reliably discriminate and localize all hepatic cells, including + a population of lipid-associated macrophages (LAMs) at the bile + ducts. We then align this atlas across seven species, revealing + the conserved program of bona fide Kupffer cells and LAMs. We + also uncover the respective spatially resolved cellular niches + of these macrophages and the microenvironmental circuits driving + their unique transcriptomic identities. We demonstrate that LAMs + are induced by local lipid exposure, leading to their induction + in steatotic regions of the murine and human liver, while + Kupffer cell development crucially depends on their cross-talk + with hepatic stellate cells via the evolutionarily conserved + ALK1-BMP9/10 axis.", + journal = "Cell", + publisher = "Elsevier BV", + volume = 185, + number = 2, + pages = "379--396.e38", + month = jan, + year = 2022, + keywords = "CITE-seq; Kupffer cell; NAFLD; across species; atlas; + lipid-associated macrophage; liver; multi-omic; proteogenomic; + spatial transcriptomics", + copyright = "http://creativecommons.org/licenses/by/4.0/", + language = "en" +} + +@ARTICLE{Habenicht2022-ae, + title = "The {C1q-ApoE} complex: A new hallmark pathology of viral + hepatitis and nonalcoholic fatty liver disease", + author = "Habenicht, Livia K L and Wang, Zhihua and Zhang, Xi and Li, + Yuanfang and Mogler, Carolin and Huspenina, Julia Slotta and + Schmid, Roland M and Weber, Christian and Mohanta, Sarajo K and + Ma, Zhe and Yin, Changjun", + abstract = "We recently identified a high-affinity C1q-ApoE complex in human + artery atherosclerotic intima lesions and in human amyloid + plaques of Alzheimer's Disease brains defining a common + pathogenetic pathway of two diverse diseases, i.e. + atherosclerosis and dementia. C1q is the initiating and + controlling protein of the classical complement cascade (CCC), + which occupies a key role in multiple acute and chronic + inflammatory tissue responses. C1q is largely produced by + myeloid cells including Kupffer cells (KCs) and subsequently + secreted into the circulation as an inactive preprotein. Its + binding partner, Apolipoprotein E (ApoE), is produced by KCs and + hepatocytes and it is also secreted into the circulation, where + it regulates essential steps of lipid transport. In addition to + its major source, ApoE can be produced by non-liver cells + including immune cells and multiple other cells depending on + local tissue contexts. To initiate the CCC cascade, C1q must be + activated by molecules as varied as oxidized lipids, amyloid + fibrils, and immune complexes. However, ApoE is mute towards + inactive C1q but binds at high-affinity to its activated form. + Specifically, our studies revealed that ApoE is a CCC-specific + checkpoint inhibitor via the formation of the C1q-ApoE complex. + We proposed that it may arise in multiple if not all + CCC-associated diseases and that its presence indicates ongoing + CCC activity. Here, we turned to the liver to examine C1q-ApoE + complexes in human B- and C-viral hepatitis and nonalcoholic + fatty liver disease (NAFLD). In addition, we used + multidrug-resistance-2 gene-knockout (Mdr2-KO) mice as a model + for inflammatory liver disease and hepatocellular carcinoma + (HCC) pathogenesis. In normal murine and human livers, KCs were + the major C1q-producing cell type while hepatocytes were the + primary ApoE-forming cell type though the C1q-ApoE complex was + rare or nonexistent. However, significant numbers of C1q-ApoE + complexes formed in both Mdr2-KO, human viral hepatitis, and + NAFLD around portal triads where immune cells had infiltrated + the liver. Additionally, high numbers of C1q-ApoE complexes + emerged in human livers in areas of extracellular lipid droplets + across the entire liver parenchyma in NAFLD-affected patients. + Thus, the C1q-ApoE complex is a new pathological hallmark of + viral hepatitis B and C and NAFLD.", + journal = "Front. Immunol.", + publisher = "Frontiers Media SA", + volume = 13, + pages = "970938", + month = oct, + year = 2022, + keywords = "C1q-ApoE complex; classical complement cascade (CCC); + hepatocellular carcinoma (HCC); nonalcoholic fatty liver disease + (NAFLD); viral hepatitis", + copyright = "https://creativecommons.org/licenses/by/4.0/", + language = "en" +} + +@ARTICLE{Dhainaut2022-ck, + title = "Spatial {CRISPR} genomics identifies regulators of the tumor + microenvironment", + author = "Dhainaut, Maxime and Rose, Samuel A and Akturk, Guray and + Wroblewska, Aleksandra and Nielsen, Sebastian R and Park, Eun + Sook and Buckup, Mark and Roudko, Vladimir and Pia, Luisanna and + Sweeney, Robert and Le Berichel, Jessica and Wilk, C Matthias + and Bektesevic, Anela and Lee, Brian H and Bhardwaj, Nina and + Rahman, Adeeb H and Baccarini, Alessia and Gnjatic, Sacha and + Pe'er, Dana and Merad, Miriam and Brown, Brian D", + abstract = "While CRISPR screens are helping uncover genes regulating many + cell-intrinsic processes, existing approaches are suboptimal for + identifying extracellular gene functions, particularly in the + tissue context. Here, we developed an approach for spatial + functional genomics called Perturb-map. We applied Perturb-map + to knock out dozens of genes in parallel in a mouse model of + lung cancer and simultaneously assessed how each knockout + influenced tumor growth, histopathology, and immune composition. + Moreover, we paired Perturb-map and spatial transcriptomics for + unbiased analysis of CRISPR-edited tumors. We found that in + Tgfbr2 knockout tumors, the tumor microenvironment (TME) was + converted to a fibro-mucinous state, and T cells excluded, + concomitant with upregulated TGF$\beta$ and TGF$\beta$-mediated + fibroblast activation, indicating that TGF$\beta$-receptor loss + on cancer cells increased TGF$\beta$ bioavailability and its + immunosuppressive effects on the TME. These studies establish + Perturb-map for functional genomics within the tissue at + single-cell resolution with spatial architecture preserved and + provide insight into how TGF$\beta$ responsiveness of cancer + cells can affect the TME.", + journal = "Cell", + publisher = "Elsevier BV", + volume = 185, + number = 7, + pages = "1223--1239.e20", + month = mar, + year = 2022, + keywords = "CRISPR screens; Socs1; TGF beta; cancer immunology; interferon + gamma; lung cancer; spatial genomics; spatial transcriptomics; + tumor clonality; tumor microenvironment", + language = "en" +} + +@ARTICLE{Ren2023-cv, + title = "Spatial transcriptomics reveals niche-specific enrichment and + vulnerabilities of radial glial stem-like cells in malignant + gliomas", + author = "Ren, Yanming and Huang, Zongyao and Zhou, Lingling and Xiao, Peng + and Song, Junwei and He, Ping and Xie, Chuanxing and Zhou, Ran + and Li, Menghan and Dong, Xiangqun and Mao, Qing and You, Chao + and Xu, Jianguo and Liu, Yanhui and Lan, Zhigang and Zhang, + Tiejun and Gan, Qi and Yang, Yuan and Chen, Tengyun and Huang, + Bowen and Yang, Xiang and Xiao, Anqi and Ou, Yun and Su, + Zhengzheng and Chen, Lu and Zhang, Yan and Ju, Yan and Zhang, + Yuekang and Wang, Yuan", + abstract = "Diffuse midline glioma-H3K27M mutant (DMG) and glioblastoma (GBM) + are the most lethal brain tumors that primarily occur in + pediatric and adult patients, respectively. Both tumors exhibit + significant heterogeneity, shaped by distinct genetic/epigenetic + drivers, transcriptional programs including RNA splicing, and + microenvironmental cues in glioma niches. However, the spatial + organization of cellular states and niche-specific regulatory + programs remain to be investigated. Here, we perform a spatial + profiling of DMG and GBM combining short- and long-read spatial + transcriptomics, and single-cell transcriptomic datasets. We + identify clinically relevant transcriptional programs, RNA + isoform diversity, and multi-cellular ecosystems across different + glioma niches. We find that while the tumor core enriches for + oligodendrocyte precursor-like cells, radial glial stem-like + (RG-like) cells are enriched in the neuron-rich invasive niche in + both DMG and GBM. Further, we identify niche-specific regulatory + programs for RG-like cells, and functionally confirm that FAM20C + mediates invasive growth of RG-like cells in a neuron-rich + microenvironment in a human neural stem cell derived orthotopic + DMG model. Together, our results provide a blueprint for + understanding the spatial architecture and niche-specific + vulnerabilities of DMG and GBM.", + journal = "Nat. Commun.", + volume = 14, + number = 1, + pages = "1028", + month = feb, + year = 2023, + language = "en" +} + +@ARTICLE{Kenney2023-tj, + title = "Multi-omics analysis identifies {IgG2b} class-switching with + {ALCAM-CD6} co-stimulation in joint-draining lymph nodes during + advanced inflammatory-erosive arthritis", + author = "Kenney, H Mark and Rangel-Moreno, Javier and Peng, Yue and Chen, + Kiana L and Bruno, Jennifer and Embong, Abdul and Pritchett, + Elizabeth and Fox, Jeffrey I and Becerril-Villanueva, Enrique and + Gamboa-Dom{\'\i}nguez, Armando and Quataert, Sally and + Muthukrishnan, Gowrishankar and Wood, Ronald W and Korman, + Benjamin D and Anolik, Jennifer H and Xing, Lianping and + Ritchlin, Christopher T and Schwarz, Edward M and Wu, Chia-Lung", + abstract = "Introduction: Defective lymphatic drainage and translocation of + B-cells in inflamed (Bin) joint-draining lymph node sinuses are + pathogenic phenomena in patients with severe rheumatoid arthritis + (RA). However, the molecular mechanisms underlying this lymphatic + dysfunction remain poorly understood. Herein, we utilized + multi-omic spatial and single-cell transcriptomics to evaluate + altered cellular composition (including lymphatic endothelial + cells, macrophages, B-cells, and T-cells) in the joint-draining + lymph node sinuses and their associated phenotypic changes and + cell-cell interactions during RA development using the tumor + necrosis factor transgenic (TNF-Tg) mouse model. Methods: + Popliteal lymph nodes (PLNs) from wild-type (n=10) and TNF-Tg + male mice with ``Early'' (5 to 6-months of age; n=6) and + ``Advanced'' (>8-months of age; n=12) arthritis were harvested + and processed for spatial transcriptomics. Single-cell RNA + sequencing (scRNAseq) was performed in PLNs from the TNF-Tg + cohorts (n=6 PLNs pooled/cohort). PLN histopathology and ELISPOT + along with ankle histology and micro-CT were evaluated. + Histopathology of human lymph nodes and synovia was performed for + clinical correlation. Results: Advanced PLN sinuses exhibited an + increased Ighg2b/Ighm expression ratio (Early 0.5 $\pm$ 0.1 vs + Advanced 1.4 $\pm$ 0.5 counts/counts; p<0.001) that significantly + correlated with reduced talus bone volumes in the afferent ankle + (R2 = 0.54, p<0.001). Integration of single-cell and spatial + transcriptomics revealed the increased IgG2b+ plasma cells + localized in MARCO+ peri-follicular medullary sinuses. A + concomitant decreased Fth1 expression (Early 2.5 $\pm$ 0.74 vs + Advanced 1.0 $\pm$ 0.50 counts, p<0.001) within Advanced PLN + sinuses was associated with accumulation of iron-laden Prussian + blue positive macrophages in lymph nodes and synovium of Advanced + TNF-Tg mice, and further validated in RA clinical samples. + T-cells were increased 8-fold in Advanced PLNs, and bioinformatic + pathway assessment identified the interaction between ALCAM+ + macrophages and CD6+ T-cells as a plausible co-stimulatory + mechanism to promote IgG2b class-switching. Discussion: + Collectively, these data support a model of flare in chronic + TNF-induced arthritis in which loss of lymphatic flow through + affected joint-draining lymph nodes facilitates the interaction + between effluxing macrophages and T-cells via ALCAM-CD6 + co-stimulation, initiating IgG2b class-switching and plasma cell + differentiation of the expanded Bin population. Future work is + warranted to investigate immunoglobulin clonality and potential + autoimmune consequences, as well as the efficacy of anti-CD6 + therapy to prevent these pathogenic events.", + journal = "Front. Immunol.", + volume = 14, + pages = "1237498", + month = aug, + year = 2023, + keywords = "B-cells; arthritis; lymph node; lymphatics; plasma cells; + single-cell RNA sequencing; spatial transcriptomics", + language = "en" +} + +@ARTICLE{Mitamura2023-pp, + title = "Spatial transcriptomics combined with single-cell + {RNA-sequencing} unravels the complex inflammatory cell network + in atopic dermatitis", + author = "Mitamura, Yasutaka and Reiger, Matthias and Kim, Juno and Xiao, + Yi and Zhakparov, Damir and Tan, Ge and R{\"u}ckert, Beate and + Rinaldi, Arturo O and Baerenfaller, Katja and Akdis, + M{\"u}beccel and Br{\"u}ggen, Marie-Charlotte and Nadeau, Kari C + and Brunner, Patrick M and Roqueiro, Damian and Traidl-Hoffmann, + Claudia and Akdis, Cezmi A", + abstract = "BACKGROUND: Atopic dermatitis (AD) is the most common chronic + inflammatory skin disease with complex pathogenesis for which + the cellular and molecular crosstalk in AD skin has not been + fully understood. METHODS: Skin tissues examined for spatial + gene expression were derived from the upper arm of 6 healthy + control (HC) donors and 7 AD patients (lesion and nonlesion). We + performed spatial transcriptomics sequencing to characterize the + cellular infiltrate in lesional skin. For single-cell analysis, + we analyzed the single-cell data from suction blister material + from AD lesions and HC skin at the antecubital fossa skin (4 ADs + and 5 HCs) and full-thickness skin biopsies (4 ADs and 2 HCs). + The multiple proximity extension assays were performed in the + serum samples from 36 AD patients and 28 HCs. RESULTS: The + single-cell analysis identified unique clusters of fibroblasts, + dendritic cells, and macrophages in the lesional AD skin. + Spatial transcriptomics analysis showed the upregulation of + COL6A5, COL4A1, TNC, and CCL19 in COL18A1-expressing fibroblasts + in the leukocyte-infiltrated areas in AD skin. CCR7-expressing + dendritic cells (DCs) showed a similar distribution in the + lesions. Additionally, M2 macrophages expressed CCL13 and CCL18 + in this area. Ligand-receptor interaction analysis of the + spatial transcriptome identified neighboring infiltration and + interaction between activated COL18A1-expressing fibroblasts, + CCL13- and CCL18-expressing M2 macrophages, CCR7- and + LAMP3-expressing DCs, and T cells. As observed in skin lesions, + serum levels of TNC and CCL18 were significantly elevated in AD, + and correlated with clinical disease severity. CONCLUSION: In + this study, we show the unknown cellular crosstalk in + leukocyte-infiltrated area in lesional skin. Our findings + provide a comprehensive in-depth knowledge of the nature of AD + skin lesions to guide the development of better treatments.", + journal = "Allergy", + publisher = "Wiley", + volume = 78, + number = 8, + pages = "2215--2231", + month = aug, + year = 2023, + keywords = "atopic dermatitis; single-cell transcriptomics; spatial + transcriptomics; targeted proteomics", + copyright = "http://creativecommons.org/licenses/by-nc/4.0/", + language = "en" +} + +@ARTICLE{Olaniru2023-dl, + title = "Single-cell transcriptomic and spatial landscapes of the + developing human pancreas", + author = "Olaniru, Oladapo Edward and Kadolsky, Ulrich and Kannambath, + Shichina and Vaikkinen, Heli and Fung, Kathy and Dhami, Pawan + and Persaud, Shanta J", + abstract = "Current differentiation protocols have not been successful in + reproducibly generating fully functional human beta cells in + vitro, partly due to incomplete understanding of human pancreas + development. Here, we present detailed transcriptomic analysis + of the various cell types of the developing human pancreas, + including their spatial gene patterns. We integrated single-cell + RNA sequencing with spatial transcriptomics at multiple + developmental time points and revealed distinct temporal-spatial + gene cascades. Cell trajectory inference identified endocrine + progenitor populations and branch-specific genes as the + progenitors differentiate toward alpha or beta cells. Spatial + differentiation trajectories indicated that Schwann cells are + spatially co-located with endocrine progenitors, and cell-cell + connectivity analysis predicted that they may interact via + L1CAM-EPHB2 signaling. Our integrated approach enabled us to + identify heterogeneity and multiple lineage dynamics within the + mesenchyme, showing that it contributed to the exocrine acinar + cell state. Finally, we have generated an interactive web + resource for investigating human pancreas development for the + research community.", + journal = "Cell Metab.", + publisher = "Elsevier BV", + volume = 35, + number = 1, + pages = "184--199.e5", + month = jan, + year = 2023, + keywords = "Schwann cells; Visium; beta cell development; endocrine + progenitors; human fetal pancreas; scRNA-seq; spatial + transcriptomics; trajectory inference", + copyright = "http://creativecommons.org/licenses/by/4.0/", + language = "en" +} + +@ARTICLE{Heezen2023-oj, + title = "Spatial transcriptomics reveal markers of histopathological + changes in Duchenne muscular dystrophy mouse models", + author = "Heezen, L G M and Abdelaal, T and van Putten, M and Aartsma-Rus, + A and Mahfouz, A and Spitali, P", + abstract = "Duchenne muscular dystrophy is caused by mutations in the DMD + gene, leading to lack of dystrophin. Chronic muscle damage + eventually leads to histological alterations in skeletal + muscles. The identification of genes and cell types driving + tissue remodeling is a key step to developing effective + therapies. Here we use spatial transcriptomics in two Duchenne + muscular dystrophy mouse models differing in disease severity to + identify gene expression signatures underlying skeletal muscle + pathology and to directly link gene expression to muscle + histology. We perform deconvolution analysis to identify cell + types contributing to histological alterations. We show + increased expression of specific genes in areas of muscle + regeneration (Myl4, Sparc, Hspg2), fibrosis (Vim, Fn1, Thbs4) + and calcification (Bgn, Ctsk, Spp1). These findings are + confirmed by smFISH. Finally, we use differentiation dynamic + analysis in the D2-mdx muscle to identify muscle fibers in the + present state that are predicted to become affected in the + future state.", + journal = "Nat. Commun.", + publisher = "Springer Science and Business Media LLC", + volume = 14, + number = 1, + pages = "4909", + month = aug, + year = 2023, + copyright = "https://creativecommons.org/licenses/by/4.0", + language = "en" +} + +@ARTICLE{Topchyan2022-vc, + title = "Spatial transcriptomics demonstrates the role of {CD4} {T} cells + in effector {CD8} {T} cell differentiation during chronic viral + infection", + author = "Topchyan, Paytsar and Zander, Ryan and Kasmani, Moujtaba Y and + Nguyen, Christine and Brown, Ashley and Lin, Siying and Burns, + Robert and Cui, Weiguo", + abstract = "CD4 T cell help is critical to sustain effector CD8 T cell + responses during chronic infection, notably via T follicular + helper (Tfh)-derived interleukin-21 (IL-21). Conversely, CD4 + depletion results in severe CD8 T cell dysfunction and lifelong + viremia despite CD4 T cell reemergence following transient + depletion. These observations suggest that repopulating CD4 + subsets are functionally or numerically insufficient to + orchestrate a robust CD8 response. We utilize spatial + transcriptomics and single-cell RNA sequencing (scRNA-seq) to + investigate CD4 T cell heterogeneity under CD4-replete and + -deplete conditions and explore cellular interactions during + chronic infection. Although IL-21-producing Tfh cells repopulate + following transient CD4 depletion, they are outnumbered by + immunomodulatory CD4 T cells. Moreover, the splenic architecture + appears perturbed, with decreases in white pulp regions, + coinciding with germinal center losses. These disruptions in + splenic architecture are associated with diminished Tfh and + progenitor CD8 T cell colocalization, providing a potential + mechanism for impaired progenitor-to-effector CD8 T cell + differentiation during ``un-helped'' conditions.", + journal = "Cell Rep.", + publisher = "Elsevier BV", + volume = 41, + number = 9, + pages = "111736", + month = nov, + year = 2022, + keywords = "CD4 T cells; CD8 T cells; CP: Immunology; IL-21; LCMV; T + follicular helper cells; single-cell RNA sequencing; spatial + transcriptomics", + copyright = "http://creativecommons.org/licenses/by-nc-nd/4.0/", + language = "en" +} + +@ARTICLE{Filipescu2023-tl, + title = "{MacroH2A} restricts inflammatory gene expression in melanoma + cancer-associated fibroblasts by coordinating chromatin looping", + author = "Filipescu, Dan and Carcamo, Saul and Agarwal, Aman and Tung, + Navpreet and Humblin, {\'E}tienne and Goldberg, Matthew S and + Vyas, Nikki S and Beaumont, Kristin G and Demircioglu, Deniz and + Sridhar, Subhasree and Ghiraldini, Flavia G and Capparelli, + Claudia and Aplin, Andrew E and Salmon, H{\'e}l{\`e}ne and + Sebra, Robert and Kamphorst, Alice O and Merad, Miriam and + Hasson, Dan and Bernstein, Emily", + abstract = "MacroH2A has established tumour suppressive functions in + melanoma and other cancers, but an unappreciated role in the + tumour microenvironment. Using an autochthonous, immunocompetent + mouse model of melanoma, we demonstrate that mice devoid of + macroH2A variants exhibit increased tumour burden compared with + wild-type counterparts. MacroH2A-deficient tumours accumulate + immunosuppressive monocytes and are depleted of functional + cytotoxic T cells, characteristics consistent with a compromised + anti-tumour response. Single cell and spatial transcriptomics + identify increased dedifferentiation along the neural crest + lineage of the tumour compartment and increased frequency and + activation of cancer-associated fibroblasts following macroH2A + loss. Mechanistically, macroH2A-deficient cancer-associated + fibroblasts display increased myeloid chemoattractant activity + as a consequence of hyperinducible expression of inflammatory + genes, which is enforced by increased chromatin looping of their + promoters to enhancers that gain H3K27ac. In summary, we reveal + a tumour suppressive role for macroH2A variants through the + regulation of chromatin architecture in the tumour stroma with + potential implications for human melanoma.", + journal = "Nat. Cell Biol.", + publisher = "Springer Science and Business Media LLC", + volume = 25, + number = 9, + pages = "1332--1345", + month = sep, + year = 2023, + copyright = "https://creativecommons.org/licenses/by/4.0", + language = "en" +} + +@ARTICLE{Vanrobaeys2023-zc, + title = "Mapping the spatial transcriptomic signature of the hippocampus + during memory consolidation", + author = "Vanrobaeys, Yann and Mukherjee, Utsav and Langmack, Lucy and + Beyer, Stacy E and Bahl, Ethan and Lin, Li-Chun and Michaelson, + Jacob J and Abel, Ted and Chatterjee, Snehajyoti", + abstract = "Memory consolidation involves discrete patterns of + transcriptional events in the hippocampus. Despite the emergence + of single-cell transcriptomic profiling techniques, mapping the + transcriptomic signature across subregions of the hippocampus + has remained challenging. Here, we utilized unbiased spatial + sequencing to delineate transcriptome-wide gene expression + changes across subregions of the dorsal hippocampus of male mice + following learning. We find that each subregion of the + hippocampus exhibits distinct yet overlapping transcriptomic + signatures. The CA1 region exhibited increased expression of + genes related to transcriptional regulation, while the DG showed + upregulation of genes associated with protein folding. + Importantly, our approach enabled us to define the + transcriptomic signature of learning within two less-defined + hippocampal subregions, CA1 stratum radiatum, and oriens. We + demonstrated that CA1 subregion-specific expression of a + transcription factor subfamily has a critical functional role in + the consolidation of long-term memory. This work demonstrates + the power of spatial molecular approaches to reveal simultaneous + transcriptional events across the hippocampus during memory + consolidation.", + journal = "Nat. Commun.", + publisher = "Springer Science and Business Media LLC", + volume = 14, + number = 1, + pages = "6100", + month = sep, + year = 2023, + copyright = "https://creativecommons.org/licenses/by/4.0", + language = "en" +} + +@ARTICLE{Kasmani2023-bp, + title = "A spatial sequencing atlas of age-induced changes in the lung + during influenza infection", + author = "Kasmani, Moujtaba Y and Topchyan, Paytsar and Brown, Ashley K + and Brown, Ryan J and Wu, Xiaopeng and Chen, Yao and Khatun, + Achia and Alson, Donia and Wu, Yue and Burns, Robert and Lin, + Chien-Wei and Kudek, Matthew R and Sun, Jie and Cui, Weiguo", + abstract = "Influenza virus infection causes increased morbidity and + mortality in the elderly. Aging impairs the immune response to + influenza, both intrinsically and because of altered + interactions with endothelial and pulmonary epithelial cells. To + characterize these changes, we performed single-cell RNA + sequencing (scRNA-seq), spatial transcriptomics, and bulk RNA + sequencing (bulk RNA-seq) on lung tissue from young and aged + female mice at days 0, 3, and 9 post-influenza infection. Our + analyses identified dozens of key genes differentially expressed + in kinetic, age-dependent, and cell type-specific manners. Aged + immune cells exhibited altered inflammatory, memory, and + chemotactic profiles. Aged endothelial cells demonstrated + characteristics of reduced vascular wound healing and a + prothrombotic state. Spatial transcriptomics identified novel + profibrotic and antifibrotic markers expressed by epithelial and + non-epithelial cells, highlighting the complex networks that + promote fibrosis in aged lungs. Bulk RNA-seq generated a + timeline of global transcriptional activity, showing increased + expression of genes involved in inflammation and coagulation in + aged lungs. Our work provides an atlas of high-throughput + sequencing methodologies that can be used to investigate + age-related changes in the response to influenza virus, identify + novel cell-cell interactions for further study, and ultimately + uncover potential therapeutic targets to improve health outcomes + in the elderly following influenza infection.", + journal = "Nat. Commun.", + publisher = "Springer Science and Business Media LLC", + volume = 14, + number = 1, + pages = "6597", + month = oct, + year = 2023, + copyright = "https://creativecommons.org/licenses/by/4.0", + language = "en" +} + +@ARTICLE{Castranio2023-gp, + title = "Microglial {INPP5D} limits plaque formation and glial reactivity + in the {PSAPP} mouse model of Alzheimer's disease", + author = "Castranio, Emilie L and Hasel, Philip and Haure-Mirande, + Jean-Vianney and Ramirez Jimenez, Angie V and Hamilton, B Wade + and Kim, Rachel D and Glabe, Charles G and Wang, Minghui and + Zhang, Bin and Gandy, Sam and Liddelow, Shane A and Ehrlich, + Michelle E", + abstract = "INTRODUCTION: The inositol polyphosphate-5-phosphatase D + (INPP5D) gene encodes a dual-specificity phosphatase that can + dephosphorylate both phospholipids and phosphoproteins. Single + nucleotide polymorphisms in INPP5D impact risk for developing + late onset sporadic Alzheimer's disease (LOAD). METHODS: To + assess the consequences of inducible Inpp5d knockdown in + microglia of APPKM670/671NL /PSEN1$\Delta$exon9 (PSAPP) mice, we + injected 3-month-old Inpp5dfl/fl /Cx3cr1CreER/+ and + PSAPP/Inpp5dfl/fl /Cx3cr1CreER/+ mice with either tamoxifen + (TAM) or corn oil (CO) to induce recombination. RESULTS: At age + 6 months, we found that the percent area of 6E10+ deposits and + plaque-associated microglia in Inpp5d knockdown mice were + increased compared to controls. Spatial transcriptomics + identified a plaque-specific expression profile that was + extensively altered by Inpp5d knockdown. DISCUSSION: These + results demonstrate that conditional Inpp5d downregulation in + the PSAPP mouse increases plaque burden and recruitment of + microglia to plaques. Spatial transcriptomics highlighted an + extended gene expression signature associated with plaques and + identified CST7 (cystatin F) as a novel marker of plaques. + HIGHLIGHTS: Inpp5d knockdown increases plaque burden and + plaque-associated microglia number. Spatial transcriptomics + identifies an expanded plaque-specific gene expression profile. + Plaque-induced gene expression is altered by Inpp5d knockdown in + microglia. Our plaque-associated gene signature overlaps with + human Alzheimer's disease gene networks.", + journal = "Alzheimers. Dement.", + publisher = "Wiley", + volume = 19, + number = 6, + pages = "2239--2252", + month = jun, + year = 2023, + keywords = "Alzheimer's disease; Inpp5d; SHIP1; cystatin F; microglia; + oligomer; spatial transcriptomics", + copyright = "http://creativecommons.org/licenses/by-nc-nd/4.0/", + language = "en" +} + +@ARTICLE{Barkley2022-wm, + title = "Cancer cell states recur across tumor types and form specific + interactions with the tumor microenvironment", + author = "Barkley, Dalia and Moncada, Reuben and Pour, Maayan and + Liberman, Deborah A and Dryg, Ian and Werba, Gregor and Wang, + Wei and Baron, Maayan and Rao, Anjali and Xia, Bo and Fran{\c + c}a, Gustavo S and Weil, Alejandro and Delair, Deborah F and + Hajdu, Cristina and Lund, Amanda W and Osman, Iman and Yanai, + Itai", + abstract = "Transcriptional heterogeneity among malignant cells of a tumor + has been studied in individual cancer types and shown to be + organized into cancer cell states; however, it remains unclear + to what extent these states span tumor types, constituting + general features of cancer. Here, we perform a pan-cancer + single-cell RNA-sequencing analysis across 15 cancer types and + identify a catalog of gene modules whose expression defines + recurrent cancer cell states including 'stress', 'interferon + response', 'epithelial-mesenchymal transition', 'metal + response', 'basal' and 'ciliated'. Spatial transcriptomic + analysis linked the interferon response in cancer cells to T + cells and macrophages in the tumor microenvironment. Using mouse + models, we further found that induction of the interferon + response module varies by tumor location and is diminished upon + elimination of lymphocytes. Our work provides a framework for + studying how cancer cell states interact with the tumor + microenvironment to form organized systems capable of immune + evasion, drug resistance and metastasis.", + journal = "Nat. Genet.", + publisher = "Springer Science and Business Media LLC", + volume = 54, + number = 8, + pages = "1192--1201", + month = aug, + year = 2022, + language = "en" +} + +@ARTICLE{Eum2024-gk, + title = "Single-cell {RNA} sequencing reveals myeloid and {T} cell + co-stimulation mediated by {IL-7} anti-cancer immunotherapy", + author = "Eum, Hye Hyeon and Jeong, Dasom and Kim, Nayoung and Jo, Areum + and Na, Minsu and Kang, Huiram and Hong, Yourae and Kong, Jin-Sun + and Jeong, Gi Heon and Yoo, Seung-Ah and Lee, Hae-Ock", + abstract = "BACKGROUND: Immune checkpoint inhibitors unleash inhibitory + signals on T cells conferred by tumors and surrounding stromal + cells. Despite the clinical efficacy of checkpoint inhibitors, + the lack of target expression and persistence of + immunosuppressive cells limit the pervasive effectiveness of the + therapy. These limitations may be overcome by alternative + approaches that co-stimulate T cells and the immune + microenvironment. METHODS: We analyzed single-cell RNA sequencing + data from multiple human cancers and a mouse tumor transplant + model to discover the pleiotropic expression of the Interleukin 7 + (IL-7) receptor on T cells, macrophages, and dendritic cells. + RESULTS: Our experiment on the mouse model demonstrated that + recombinant IL-7 therapy induces tumor regression, expansion of + effector CD8 T cells, and pro-inflammatory activation of + macrophages. Moreover, spatial transcriptomic data support + immunostimulatory interactions between macrophages and T cells. + CONCLUSION: These results indicate that IL-7 therapy induces + anti-tumor immunity by activating T cells and pro-inflammatory + myeloid cells, which may have diverse therapeutic applicability.", + journal = "Br. J. Cancer", + month = feb, + year = 2024, + language = "en" +} + +@ARTICLE{Canela2023-sa, + title = "A spatially anchored transcriptomic atlas of the human kidney + papilla identifies significant immune injury in patients with + stone disease", + author = "Canela, Victor Hugo and Bowen, William S and Ferreira, Ricardo + Melo and Syed, Farooq and Lingeman, James E and Sabo, Angela R + and Barwinska, Daria and Winfree, Seth and Lake, Blue B and + Cheng, Ying-Hua and Gaut, Joseph P and Ferkowicz, Michael and + LaFavers, Kaice A and Zhang, Kun and Coe, Fredric L and + Worcester, Elaine and {Kidney Precision Medicine Project} and + Jain, Sanjay and Eadon, Michael T and Williams, Jr, James C and + El-Achkar, Tarek M", + abstract = "Kidney stone disease causes significant morbidity and increases + health care utilization. In this work, we decipher the cellular + and molecular niche of the human renal papilla in patients with + calcium oxalate (CaOx) stone disease and healthy subjects. In + addition to identifying cell types important in papillary + physiology, we characterize collecting duct cell subtypes and an + undifferentiated epithelial cell type that was more prevalent in + stone patients. Despite the focal nature of mineral deposition in + nephrolithiasis, we uncover a global injury signature + characterized by immune activation, oxidative stress and + extracellular matrix remodeling. We also identify the association + of MMP7 and MMP9 expression with stone disease and mineral + deposition, respectively. MMP7 and MMP9 are significantly + increased in the urine of patients with CaOx stone disease, and + their levels correlate with disease activity. Our results define + the spatial molecular landscape and specific pathways + contributing to stone-mediated injury in the human papilla and + identify associated urinary biomarkers.", + journal = "Nat. Commun.", + volume = 14, + number = 1, + pages = "4140", + month = jul, + year = 2023, + language = "en" +} + +@ARTICLE{Garbarino2023-uw, + title = "Spatial resolution of cellular senescence dynamics in human + colorectal liver metastasis", + author = "Garbarino, Ombretta and Lambroia, Luca and Basso, Gianluca and + Marrella, Veronica and Franceschini, Barbara and Soldani, + Cristiana and Pasqualini, Fabio and Giuliano, Desiree and Costa, + Guido and Peano, Clelia and Barbarossa, Davide and Annarita, + Destro and Salvati, Andreina and Terracciano, Luigi and Torzilli, + Guido and Donadon, Matteo and Faggioli, Francesca", + abstract = "Hepatic metastasis is a clinical challenge for colorectal cancer + (CRC). Senescent cancer cells accumulate in CRC favoring tumor + dissemination. Whether this mechanism progresses also in + metastasis is unexplored. Here, we integrated spatial + transcriptomics, 3D-microscopy, and multicellular transcriptomics + to study the role of cellular senescence in human colorectal + liver metastasis (CRLM). We discovered two distinct senescent + metastatic cancer cell (SMCC) subtypes, transcriptionally located + at the opposite pole of epithelial (e) to mesenchymal (m) + transition. SMCCs differ in chemotherapy susceptibility, + biological program, and prognostic roles. Mechanistically, + epithelial (e)SMCC initiation relies on nucleolar stress, whereby + c-myc dependent oncogene hyperactivation induces ribosomal RPL11 + accumulation and DNA damage response. In a 2D pre-clinical model, + we demonstrated that RPL11 co-localized with HDM2, a p53-specific + ubiquitin ligase, leading to senescence activation in (e)SMCCs. + On the contrary, mesenchymal (m)SMCCs undergo TGF$\beta$ + paracrine activation of NOX4-p15 effectors. SMCCs display + opposing effects also in the immune regulation of neighboring + cells, establishing an immunosuppressive environment or leading + to an active immune workflow. Both SMCC signatures are predictive + biomarkers whose unbalanced ratio determined the clinical outcome + in CRLM and CRC patients. Altogether, we provide a comprehensive + new understanding of the role of SMCCs in CRLM and highlight + their potential as new therapeutic targets to limit CRLM + progression.", + journal = "Aging Cell", + volume = 22, + number = 7, + pages = "e13853", + month = jul, + year = 2023, + keywords = "EMT; cellular senescence; colorectal cancer liver metastasis; + prognostic role; senescence-associated secretory phenotype; + spatial transcriptomics", + language = "en" +} + +@ARTICLE{Caetano2023-kj, + title = "Spatially resolved transcriptomics reveals pro-inflammatory + fibroblast involved in lymphocyte recruitment through {CXCL8} + and {CXCL10}", + author = "Caetano, Ana J and Redhead, Yushi and Karim, Farah and Dhami, + Pawan and Kannambath, Shichina and Nuamah, Rosamond and Volponi, + Ana A and Nibali, Luigi and Booth, Veronica and D'Agostino, + Eleanor M and Sharpe, Paul T", + abstract = "The interplay among different cells in a tissue is essential for + maintaining homeostasis. Although disease states have been + traditionally attributed to individual cell types, increasing + evidence and new therapeutic options have demonstrated the + primary role of multicellular functions to understand health and + disease, opening new avenues to understand pathogenesis and + develop new treatment strategies. We recently described the + cellular composition and dynamics of the human oral mucosa; + however, the spatial arrangement of cells is needed to better + understand a morphologically complex tissue. Here, we link + single-cell RNA sequencing, spatial transcriptomics, and + high-resolution multiplex fluorescence in situ hybridisation to + characterise human oral mucosa in health and oral chronic + inflammatory disease. We deconvolved expression for resolution + enhancement of spatial transcriptomic data and defined highly + specialised epithelial and stromal compartments describing + location-specific immune programs. Furthermore, we spatially + mapped a rare pathogenic fibroblast population localised in a + highly immunogenic region, responsible for lymphocyte + recruitment through CXCL8 and CXCL10 and with a possible role in + pathological angiogenesis through ALOX5AP. Collectively, our + study provides a comprehensive reference for the study of oral + chronic disease pathogenesis.", + journal = "Elife", + publisher = "eLife Sciences Publications, Ltd", + volume = 12, + month = jan, + year = 2023, + keywords = "cell biology; fibroblast; gingiva; human; immunology; + inflammation; oral mucosa; periodontal disease; spatial genomics", + copyright = "http://creativecommons.org/licenses/by/4.0/", + language = "en" +} + +@ARTICLE{Tung2023-oi, + title = "Spatiotemporal signaling underlies progressive vascular + rarefaction in myocardial infarction", + author = "Tung, Lin Wei and Groppa, Elena and Soliman, Hesham and Lin, + Bruce and Chang, Chihkai and Cheung, Chun Wai and Ritso, Morten + and Guo, David and Rempel, Lucas and Sinha, Sarthak and Eisner, + Christine and Brassard, Julyanne and McNagny, Kelly and + Biernaskie, Jeff and Rossi, Fabio", + abstract = "Therapeutic angiogenesis represents a promising avenue to + revascularize the ischemic heart. Its limited success is partly + due to our poor understanding of the cardiac stroma, specifically + mural cells, and their response to ischemic injury. Here, we + combine single-cell and positional transcriptomics to assess the + behavior of mural cells within the healing heart. In response to + myocardial infarction, mural cells adopt an altered state closely + associated with the infarct and retain a distinct lineage from + fibroblasts. This response is concurrent with vascular + rarefaction and reduced vascular coverage by mural cells. + Positional transcriptomics reveals that the infarcted heart is + governed by regional-dependent and temporally regulated programs. + While the remote zone acts as an important source of + pro-angiogenic signals, the infarct zone is accentuated by + chronic activation of anti-angiogenic, pro-fibrotic, and + inflammatory cues. Together, our work unveils the spatiotemporal + programs underlying cardiac repair and establishes an association + between vascular deterioration and mural cell dysfunction.", + journal = "Nat. Commun.", + volume = 14, + number = 1, + pages = "8498", + month = dec, + year = 2023, + language = "en" +} + +% The entry below contains non-ASCII chars that could not be converted +% to a LaTeX equivalent. +@ARTICLE{Heimli2022-lj, + title = "Multimodal human thymic profiling reveals trajectories and + cellular milieu for {T} agonist selection", + author = "Heimli, Marte and Fl{\aa}m, Siri Tenneb{\o} and Hjorthaug, Hanne + Sagsveen and Trinh, Don and Frisk, Michael and Dumont, + Karl-Andreas and Ribarska, Teodora and Tekpli, Xavier and Saare, + Mario and Lie, Benedicte Alexandra", + abstract = "To prevent autoimmunity, thymocytes expressing self-reactive T + cell receptors (TCRs) are negatively selected, however, + divergence into tolerogenic, agonist selected lineages represent + an alternative fate. As thymocyte development, selection, and + lineage choices are dependent on spatial context and cell-to-cell + interactions, we have performed Cellular Indexing of + Transcriptomes and Epitopes by sequencing (CITE-seq) and spatial + transcriptomics on paediatric human thymu​​s. Thymocytes + expressing markers of strong TCR signalling diverged from the + conventional developmental trajectory prior to CD4+ or CD8+ + lineage commitment, while markers of different agonist selected T + cell populations (CD8$\alpha$$\alpha$(I), + CD8$\alpha$$\alpha$(II), T(agonist), Treg(diff), and Treg) + exhibited variable timing of induction. Expression profiles of + chemokines and co-stimulatory molecules, together with spatial + localisation, supported that dendritic cells, B cells, and + stromal cells contribute to agonist selection, with different + subsets influencing thymocytes at specific developmental stages + within distinct spatial niches. Understanding factors influencing + agonist T cells is needed to benefit from their immunoregulatory + effects in clinical use.", + journal = "Front. Immunol.", + volume = 13, + pages = "1092028", + year = 2022, + keywords = "T agonist selection; T cell development; antigen-presenting + cells; autoimmunity; human thymus; multi-modal; single-cell RNA + sequencing; spatial transcriptomics", + language = "en" +} + +@ARTICLE{Arora2023-px, + title = "Spatial transcriptomics reveals distinct and conserved tumor + core and edge architectures that predict survival and targeted + therapy response", + author = "Arora, Rohit and Cao, Christian and Kumar, Mehul and Sinha, + Sarthak and Chanda, Ayan and McNeil, Reid and Samuel, Divya and + Arora, Rahul K and Matthews, T Wayne and Chandarana, Shamir and + Hart, Robert and Dort, Joseph C and Biernaskie, Jeff and Neri, + Paola and Hyrcza, Martin D and Bose, Pinaki", + abstract = "The spatial organization of the tumor microenvironment has a + profound impact on biology and therapy response. Here, we + perform an integrative single-cell and spatial transcriptomic + analysis on HPV-negative oral squamous cell carcinoma (OSCC) to + comprehensively characterize malignant cells in tumor core (TC) + and leading edge (LE) transcriptional architectures. We show + that the TC and LE are characterized by unique transcriptional + profiles, neighboring cellular compositions, and ligand-receptor + interactions. We demonstrate that the gene expression profile + associated with the LE is conserved across different cancers + while the TC is tissue specific, highlighting common mechanisms + underlying tumor progression and invasion. Additionally, we find + our LE gene signature is associated with worse clinical outcomes + while TC gene signature is associated with improved prognosis + across multiple cancer types. Finally, using an in silico + modeling approach, we describe spatially-regulated patterns of + cell development in OSCC that are predictably associated with + drug response. Our work provides pan-cancer insights into TC and + LE biology and interactive spatial atlases ( + http://www.pboselab.ca/spatial\_OSCC/ ; + http://www.pboselab.ca/dynamo\_OSCC/ ) that can be foundational + for developing novel targeted therapies.", + journal = "Nat. Commun.", + publisher = "Springer Science and Business Media LLC", + volume = 14, + number = 1, + pages = "5029", + month = aug, + year = 2023, + copyright = "https://creativecommons.org/licenses/by/4.0", + language = "en" +} + +@ARTICLE{Chen2023-ci, + title = "Human neural stem cells restore spatial memory in a transgenic + Alzheimer's disease mouse model by an immunomodulating mechanism", + author = "Chen, Kevin S and Noureldein, Mohamed H and McGinley, Lisa M and + Hayes, John M and Rigan, Diana M and Kwentus, Jacquelin F and + Mason, Shayna N and Mendelson, Faye E and Savelieff, Masha G and + Feldman, Eva L", + abstract = "Introduction: Stem cells are a promising therapeutic in + Alzheimer's disease (AD) given the complex pathophysiologic + pathways involved. However, the therapeutic mechanisms of stem + cells remain unclear. Here, we used spatial transcriptomics to + elucidate therapeutic mechanisms of human neural stem cells + (hNSCs) in an animal model of AD. Methods: hNSCs were + transplanted into the fimbria fornix of the hippocampus using the + 5XFAD mouse model. Spatial memory was assessed by Morris water + maze. Amyloid plaque burden was quantified. Spatial + transcriptomics was performed and differentially expressed genes + (DEGs) identified both globally and within the hippocampus. + Subsequent pathway enrichment and ligand-receptor network + analysis was performed. Results: hNSC transplantation restored + learning curves of 5XFAD mice. However, there were no changes in + amyloid plaque burden. Spatial transcriptomics showed 1,061 DEGs + normalized in hippocampal subregions. Plaque induced genes in + microglia, along with populations of stage 1 and stage 2 disease + associated microglia (DAM), were normalized upon hNSC + transplantation. Pathologic signaling between hippocampus and DAM + was also restored. Discussion: hNSCs normalized many dysregulated + genes, although this was not mediated by a change in amyloid + plaque levels. Rather, hNSCs appear to exert beneficial effects + in part by modulating microglia-mediated neuroinflammation and + signaling in AD.", + journal = "Front. Aging Neurosci.", + volume = 15, + pages = "1306004", + month = dec, + year = 2023, + keywords = "Alzheimer's disease; cell communication; disease-associated + microglia; immunomodulation; microglia; neural stem cell; spatial + transcriptomics; stem cell therapy", + language = "en" +} + +@ARTICLE{Mauduit2022-hu, + title = "Spatial transcriptomics of the lacrimal gland features + macrophage activity and epithelium metabolism as key alterations + during chronic inflammation", + author = "Mauduit, Olivier and Delcroix, Vanessa and Umazume, Takeshi and + de Paiva, Cintia S and Dartt, Darlene A and Makarenkova, Helen P", + abstract = "The lacrimal gland (LG) is an exocrine gland that produces the + watery part of the tear film that lubricates the ocular surface. + Chronic inflammation, such as Sj{\"o}gren's syndrome (SS), is + one of the leading causes of aqueous-deficiency dry eye (ADDE) + disease worldwide. In this study we analyzed the chronic + inflammation in the LGs of the NOD.B10Sn-H2b/J (NOD.H-2b) mice, + a mouse model of SS, utilizing bulk RNAseq and Visium spatial + gene expression. With Seurat we performed unsupervised + clustering and analyzed the spatial cell distribution and gene + expression changes in all cell clusters within the LG sections. + Moreover, for the first time, we analyzed and validated specific + pathways defined by bulk RNAseq using Visium technology to + determine activation of these pathways within the LG sections. + This analysis suggests that altered metabolism and the hallmarks + of inflammatory responses from both epithelial and immune cells + drive inflammation. The most significant pathway enriched in + upregulated DEGs was the ``TYROBP Causal Network'', that has not + been described previously in SS. We also noted a significant + decrease in lipid metabolism in the LG of the NOD.H-2b mice. Our + data suggests that modulation of these pathways can provide a + therapeutic strategy to treat ADDE.", + journal = "Front. Immunol.", + publisher = "Frontiers Media SA", + volume = 13, + pages = "1011125", + month = oct, + year = 2022, + keywords = "RNA sequencing; TYROBP; chronic inflammation; lacrimal gland; + lipid metabolism; macrophages; spatial transcriptomics; visium", + copyright = "https://creativecommons.org/licenses/by/4.0/", + language = "en" +} + +@ARTICLE{Bassiouni2023-ls, + title = "Spatial transcriptomic analysis of a diverse patient cohort + reveals a conserved architecture in triple-negative breast + cancer", + author = "Bassiouni, Rania and Idowu, Michael O and Gibbs, Lee D and + Robila, Valentina and Grizzard, Pamela J and Webb, Michelle G + and Song, Jiarong and Noriega, Ashley and Craig, David W and + Carpten, John D", + abstract = "Triple-negative breast cancer (TNBC) is an aggressive disease + that disproportionately affects African American (AA) women. + Limited targeted therapeutic options exist for patients with + TNBC. Here, we employ spatial transcriptomics to interrogate + tissue from a racially diverse TNBC cohort to comprehensively + annotate the transcriptional states of spatially resolved + cellular populations. A total of 38,706 spatial features from a + cohort of 28 sections from 14 patients were analyzed. + Intratumoral analysis of spatial features from individual + sections revealed heterogeneous transcriptional substructures. + However, integrated analysis of all samples resulted in nine + transcriptionally distinct clusters that mapped across all + individual sections. Furthermore, novel use of join count + analysis demonstrated nonrandom directional spatial dependencies + of the transcriptionally defined shared clusters, supporting a + conserved spatio-transcriptional architecture in TNBC. These + findings were substantiated in an independent validation cohort + comprising 17,861 spatial features representing 15 samples from + 8 patients. Stratification of samples by race revealed + race-associated differences in hypoxic tumor content and regions + of immune-rich infiltrate. Overall, this study combined spatial + and functional molecular analyses to define the tumor + architecture of TNBC, with potential implications in + understanding TNBC disparities. SIGNIFICANCE: Spatial + transcriptomics profiling of a diverse cohort of triple-negative + breast cancers and innovative informatics approaches reveal a + conserved cellular architecture across cancers and identify + proportional differences in tumor cell composition by race.", + journal = "Cancer Res.", + publisher = "American Association for Cancer Research (AACR)", + volume = 83, + number = 1, + pages = "34--48", + month = jan, + year = 2023, + language = "en" +} + +@ARTICLE{Lyubetskaya2022-yl, + title = "Assessment of spatial transcriptomics for oncology discovery", + author = "Lyubetskaya, Anna and Rabe, Brian and Fisher, Andrew and Lewin, + Anne and Neuhaus, Isaac and Brett, Constance and Brett, Todd and + Pereira, Ethel and Golhar, Ryan and Kebede, Sami and Font-Tello, + Alba and Mosure, Kathy and Van Wittenberghe, Nicholas and + Mavrakis, Konstantinos J and MacIsaac, Kenzie and Chen, Benjamin + J and Drokhlyansky, Eugene", + abstract = "Tumor heterogeneity is a major challenge for oncology drug + discovery and development. Understanding of the spatial tumor + landscape is key to identifying new targets and impactful model + systems. Here, we test the utility of spatial transcriptomics + (ST) for oncology discovery by profiling 40 tissue sections and + 80,024 capture spots across a diverse set of tissue types, + sample formats, and RNA capture chemistries. We verify the + accuracy and fidelity of ST by leveraging matched pathology + analysis, which provides a ground truth for tissue section + composition. We then use spatial data to demonstrate the capture + of key tumor depth features, identifying hypoxia, necrosis, + vasculature, and extracellular matrix variation. We also + leverage spatial context to identify relative cell-type + locations showing the anti-correlation of tumor and immune cells + in syngeneic cancer models. Lastly, we demonstrate target + identification approaches in clinical pancreatic adenocarcinoma + samples, highlighting tumor intrinsic biomarkers and paracrine + signaling.", + journal = "Cell Rep. Methods", + publisher = "Elsevier BV", + volume = 2, + number = 11, + pages = "100340", + month = nov, + year = 2022, + keywords = "biomarkers; cancer biology; cancer genomics; digital pathology; + genomics; oncology; pancreatic cancer; spatial genomics; spatial + transcriptomics; tumors", + copyright = "http://creativecommons.org/licenses/by-nc-nd/4.0/", + language = "en" +} + +@ARTICLE{Lee2023-ng, + title = "{APOE} modulates microglial immunometabolism in response to age, + amyloid pathology, and inflammatory challenge", + author = "Lee, Sangderk and Devanney, Nicholas A and Golden, Lesley R and + Smith, Cathryn T and Schwartz, James L and Walsh, Adeline E and + Clarke, Harrison A and Goulding, Danielle S and Allenger, + Elizabeth J and Morillo-Segovia, Gabriella and Friday, Cassi M + and Gorman, Amy A and Hawkinson, Tara R and MacLean, Steven M + and Williams, Holden C and Sun, Ramon C and Morganti, Josh M and + Johnson, Lance A", + abstract = "The E4 allele of Apolipoprotein E (APOE) is associated with both + metabolic dysfunction and a heightened pro-inflammatory + response: two findings that may be intrinsically linked through + the concept of immunometabolism. Here, we combined bulk, + single-cell, and spatial transcriptomics with cell-specific and + spatially resolved metabolic analyses in mice expressing human + APOE to systematically address the role of APOE across age, + neuroinflammation, and AD pathology. RNA sequencing (RNA-seq) + highlighted immunometabolic changes across the APOE4 glial + transcriptome, specifically in subsets of metabolically distinct + microglia enriched in the E4 brain during aging or following an + inflammatory challenge. E4 microglia display increased + Hif1$\alpha$ expression and a disrupted tricarboxylic acid (TCA) + cycle and are inherently pro-glycolytic, while spatial + transcriptomics and mass spectrometry imaging highlight an + E4-specific response to amyloid that is characterized by + widespread alterations in lipid metabolism. Taken together, our + findings emphasize a central role for APOE in regulating + microglial immunometabolism and provide valuable, interactive + resources for discovery and validation research.", + journal = "Cell Rep.", + publisher = "Elsevier BV", + volume = 42, + number = 3, + pages = "112196", + month = mar, + year = 2023, + keywords = "APOE; Apolipoprotein E; CP: Neuroscience; DAM; LPS; aging; + amyloid; immunometabolism; microglia; scRNA-seq; spatial + transcriptomics", + copyright = "http://creativecommons.org/licenses/by/4.0/", + language = "en" +} + +@ARTICLE{Foster2022-uy, + title = "Multiomic analysis reveals conservation of cancer-associated + fibroblast phenotypes across species and tissue of origin", + author = "Foster, Deshka S and Januszyk, Michael and Delitto, Daniel and + Yost, Kathryn E and Griffin, Michelle and Guo, Jason and + Guardino, Nicholas and Delitto, Andrea E and Chinta, Malini and + Burcham, Austin R and Nguyen, Alan T and Bauer-Rowe, Khristian E + and Titan, Ashley L and Salhotra, Ankit and Jones, R Ellen and + da Silva, Oscar and Lindsay, Hunter G and Berry, Charlotte E and + Chen, Kellen and Henn, Dominic and Mascharak, Shamik and + Talbott, Heather E and Kim, Alexia and Nosrati, Fatemeh and + Sivaraj, Dharshan and Ransom, R Chase and Matthews, Michael and + Khan, Anum and Wagh, Dhananjay and Coller, John and Gurtner, + Geoffrey C and Wan, Derrick C and Wapnir, Irene L and Chang, + Howard Y and Norton, Jeffrey A and Longaker, Michael T", + abstract = "Cancer-associated fibroblasts (CAFs) are integral to the solid + tumor microenvironment. CAFs were once thought to be a + relatively uniform population of matrix-producing cells, but + single-cell RNA sequencing has revealed diverse CAF phenotypes. + Here, we further probed CAF heterogeneity with a comprehensive + multiomics approach. Using paired, same-cell chromatin + accessibility and transcriptome analysis, we provided an + integrated analysis of CAF subpopulations over a complex spatial + transcriptomic and proteomic landscape to identify three + superclusters: steady state-like (SSL), mechanoresponsive (MR), + and immunomodulatory (IM) CAFs. These superclusters are + recapitulated across multiple tissue types and species. + Selective disruption of underlying mechanical force or immune + checkpoint inhibition therapy results in shifts in CAF + subpopulation distributions and affected tumor growth. As such, + the balance among CAF superclusters may have considerable + translational implications. Collectively, this research expands + our understanding of CAF biology, identifying regulatory + pathways in CAF differentiation and elucidating therapeutic + targets in a species- and tumor-agnostic manner.", + journal = "Cancer Cell", + publisher = "Elsevier BV", + volume = 40, + number = 11, + pages = "1392--1406.e7", + month = nov, + year = 2022, + keywords = "ATAC-seq; CODEX; RNA-seq; cancer; fibroblasts; + mechanotransduction; multi-omics; single cell; spatial + transcriptomics", + copyright = "http://www.elsevier.com/open-access/userlicense/1.0/", + language = "en" +} + +@ARTICLE{Subramanian2024-ov, + title = "Sarcoma microenvironment cell states and ecosystems are + associated with prognosis and predict response to immunotherapy", + author = "Subramanian, Ajay and Nemat-Gorgani, Neda and Ellis-Caleo, + Timothy J and van IJzendoorn, David G P and Sears, Timothy J and + Somani, Anish and Luca, Bogdan A and Zhou, Maggie Y and Bradic, + Martina and Torres, Ileana A and Oladipo, Eniola and New, + Christin and Kenney, Deborah E and Avedian, Raffi S and Steffner, + Robert J and Binkley, Michael S and Mohler, David G and Tap, + William D and D'Angelo, Sandra P and van de Rijn, Matt and + Ganjoo, Kristen N and Bui, Nam Q and Charville, Gregory W and + Newman, Aaron M and Moding, Everett J", + abstract = "Characterization of the diverse malignant and stromal cell states + that make up soft tissue sarcomas and their correlation with + patient outcomes has proven difficult using fixed clinical + specimens. Here, we employed EcoTyper, a machine-learning + framework, to identify the fundamental cell states and cellular + ecosystems that make up sarcomas on a large scale using bulk + transcriptomes with clinical annotations. We identified and + validated 23 sarcoma-specific, transcriptionally defined cell + states, many of which were highly prognostic of patient outcomes + across independent datasets. We discovered three conserved + cellular communities or ecotypes associated with underlying + genomic alterations and distinct clinical outcomes. We show that + one ecotype defined by tumor-associated macrophages and + epithelial-like malignant cells predicts response to + immune-checkpoint inhibition but not chemotherapy and validate + our findings in an independent cohort. Our results may enable + identification of patients with soft tissue sarcomas who could + benefit from immunotherapy and help develop new therapeutic + strategies.", + journal = "Nat. Cancer", + month = mar, + year = 2024, + language = "en" +} + +@ARTICLE{Gu2022-wz, + title = "Multi-omics profiling visualizes dynamics of cardiac development + and functions", + author = "Gu, Yayun and Zhou, Yan and Ju, Sihan and Liu, Xiaofei and + Zhang, Zicheng and Guo, Jia and Gao, Jimiao and Zang, Jie and + Sun, Hao and Chen, Qi and Wang, Jinghan and Xu, Jiani and Xu, + Yiqun and Chen, Yingjia and Guo, Yueshuai and Dai, Juncheng and + Ma, Hongxia and Wang, Cheng and Jin, Guangfu and Li, Chaojun and + Xia, Yankai and Shen, Hongbing and Yang, Yang and Guo, Xuejiang + and Hu, Zhibin", + abstract = "Cardiogenesis is a tightly regulated dynamic process through a + continuum of differentiation and proliferation events. Key + factors and pathways governing this process remain incompletely + understood. Here, we investigate mice hearts from embryonic day + 10.5 to postnatal week 8 and dissect developmental changes in + phosphoproteome-, proteome-, metabolome-, and + transcriptome-encompassing cardiogenesis and cardiac maturation. + We identify mitogen-activated protein kinases as core kinases + involved in transcriptional regulation by mediating the + phosphorylation of chromatin remodeling proteins during early + cardiogenesis. We construct the reciprocal regulatory network of + transcription factors (TFs) and identify a series of TFs + controlling early cardiogenesis involved in cycling-dependent + proliferation. After birth, we identify cardiac resident + macrophages with high arachidonic acid metabolism activities + likely involved in the clearance of injured apoptotic + cardiomyocytes. Together, our comprehensive multi-omics data + offer a panoramic view of cardiac development and maturation + that provides a resource for further in-depth functional + exploration.", + journal = "Cell Rep.", + publisher = "Elsevier BV", + volume = 41, + number = 13, + pages = "111891", + month = dec, + year = 2022, + keywords = "CP: Developmental biology; cardiac maturation; cardiogenesis; + efferocytosis; macrophages; multi-omics; protein + phosphorylation; transcriptional regulation", + copyright = "http://creativecommons.org/licenses/by-nc-nd/4.0/", + language = "en" +} + +@ARTICLE{Coutant2023-jt, + title = "Spatial transcriptomics reveal pitfalls and opportunities for + the detection of rare high-plasticity breast cancer subtypes", + author = "Coutant, Ang{\`e}le and Cockenpot, Vincent and Muller, Lauriane + and Degletagne, Cyril and Pommier, Roxane and Tonon, Laurie and + Ardin, Maude and Michallet, Marie-C{\'e}cile and Caux, + Christophe and Laurent, Marie and Morel, Anne-Pierre and + Saintigny, Pierre and Puisieux, Alain and Ouzounova, Maria and + Martinez, Pierre", + abstract = "Breast cancer is one of the most prominent types of cancers, in + which therapeutic resistance is a major clinical concern. + Specific subtypes, such as claudin-low and metaplastic breast + carcinoma (MpBC), have been associated with high nongenetic + plasticity, which can facilitate resistance. The similarities + and differences between these orthogonal subtypes, identified by + molecular and histopathological analyses, respectively, remain + insufficiently characterized. Furthermore, adequate methods to + identify high-plasticity tumors to better anticipate resistance + are lacking. Here, we analyzed 11 triple-negative breast tumors, + including 3 claudin-low and 4 MpBC, via high-resolution spatial + transcriptomics. We combined pathological annotations and + deconvolution approaches to precisely identify tumor spots, on + which we performed signature enrichment, differential + expression, and copy number analyses. We used The Cancer Genome + Atlas and Cancer Cell Line Encyclopedia public databases for + external validation of expression markers. By focusing our + spatial transcriptomic analyses on tumor cells in MpBC samples, + we bypassed the negative impact of stromal contamination and + identified specific markers that are neither expressed in other + breast cancer subtypes nor expressed in stromal cells. Three + markers (BMPER, POPDC3, and SH3RF3) were validated in external + expression databases encompassing bulk tumor material and + stroma-free cell lines. We unveiled that existing bulk + expression signatures of high-plasticity breast cancers are + relevant in mesenchymal transdifferentiated compartments but can + be hindered by abundant stromal cells in tumor samples, + negatively impacting their clinical applicability. Spatial + transcriptomic analyses constitute powerful tools to identify + specific expression markers and could thus enhance diagnosis and + clinical care of rare high-plasticity breast cancers.", + journal = "Lab. Invest.", + publisher = "Elsevier BV", + volume = 103, + number = 12, + pages = "100258", + month = dec, + year = 2023, + keywords = "diagnostic markers; integrative approaches; plasticity; rare + subtypes; spatial transcriptomics", + copyright = "http://creativecommons.org/licenses/by-nc-nd/4.0/", + language = "en" +} + +@ARTICLE{Sanders2022-wz, + title = "Small cell carcinoma of the ovary hypercalcemic type ({SCCOHT)}: + A review and novel case with dual germline {SMARCA4} and {BRCA2} + mutations", + author = "Sanders, Brooke E and Wolsky, Rebecca and Doughty, Elizabeth S + and Wells, Kristen L and Ghosh, Debashis and Ku, Lisa and + Pressey, Joseph G and Bitler, Benjamin B and Brubaker, Lindsay W", + abstract = "Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is + a rare and aggressive disease. While classically linked to + mutations in SMARCA4, we describe a case in a patient with both + SMARCA4 and BRCA2 germline mutations. We describe her disease + presentation, histopathology and treatment with adjuvant + systemic chemotherapy, interval hyperthermic intraperitoneal + chemotherapy, high dose chemotherapy with stem cell rescue, and + maintenance with a poly-ADP-ribose polymerase inhibitor (PARPi). + Additionally, we share spatial transcriptomics completed on + original tumor.", + journal = "Gynecol. Oncol. Rep.", + publisher = "Elsevier BV", + volume = 44, + number = 101077, + pages = "101077", + month = dec, + year = 2022, + keywords = "PARP inhibitor; Small cell carcinoma of the ovary; + Transcriptomics", + copyright = "http://creativecommons.org/licenses/by-nc-nd/4.0/", + language = "en" +} + +@ARTICLE{Akiyama2023-oh, + title = "Stromal reprogramming through dual {PDGFR$\alpha$/$\beta$} + blockade boosts the efficacy of {anti-PD-1} immunotherapy in + fibrotic tumors", + author = "Akiyama, Takahiko and Yasuda, Tadahito and Uchihara, Tomoyuki + and Yasuda-Yoshihara, Noriko and Tan, Benjy J Y and Yonemura, + Atsuko and Semba, Takashi and Yamasaki, Juntaro and Komohara, + Yoshihiro and Ohnishi, Koji and Wei, Feng and Fu, Lingfeng and + Zhang, Jun and Kitamura, Fumimasa and Yamashita, Kohei and Eto, + Kojiro and Iwagami, Shiro and Tsukamoto, Hirotake and Umemoto, + Terumasa and Masuda, Mari and Nagano, Osamu and Satou, Yorifumi + and Saya, Hideyuki and Tan, Patrick and Baba, Hideo and + Ishimoto, Takatsugu", + abstract = "Excess stroma and cancer-associated fibroblasts (CAF) enhance + cancer progression and facilitate immune evasion. Insights into + the mechanisms by which the stroma manipulates the immune + microenvironment could help improve cancer treatment. Here, we + aimed to elucidate potential approaches for stromal + reprogramming and improved cancer immunotherapy. + Platelet-derived growth factor C (PDGFC) and D expression were + significantly associated with a poor prognosis in patients with + gastric cancer, and PDGF receptor beta (PDGFR$\beta$) was + predominantly expressed in diffuse-type gastric cancer stroma. + CAFs stimulated with PDGFs exhibited markedly increased + expression of CXCL1, CXCL3, CXCL5, and CXCL8, which are involved + in polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) + recruitment. Fibrotic gastric cancer xenograft tumors exhibited + increased PMN-MDSC accumulation and decreased lymphocyte + infiltration, as well as resistance to anti-PD-1. Single-cell + RNA sequencing and spatial transcriptomics revealed that + PDGFR$\alpha$/$\beta$ blockade reversed the immunosuppressive + microenvironment through stromal modification. Finally, + combining PDGFR$\alpha$/$\beta$ blockade and anti-PD-1 treatment + synergistically suppressed the growth of fibrotic tumors. These + findings highlight the impact of stromal reprogramming on immune + reactivation and the potential for combined immunotherapy for + patients with fibrotic cancer. SIGNIFICANCE: Stromal targeting + with PDGFR$\alpha$/$\beta$ dual blockade reverses the + immunosuppressive microenvironment and enhances the efficacy of + immune checkpoint inhibitors in fibrotic cancer. See related + commentary by Tauriello, p. 655.", + journal = "Cancer Res.", + publisher = "American Association for Cancer Research (AACR)", + volume = 83, + number = 5, + pages = "753--770", + month = mar, + year = 2023, + language = "en" +} + +@ARTICLE{Yoshitake2024-qi, + title = "Molecular features of luminal breast cancer defined through + spatial and single-cell transcriptomics", + author = "Yoshitake, Ryohei and Mori, Hitomi and Ha, Desiree and Wu, Xiwei + and Wang, Jinhui and Wang, Xiaoqiang and Saeki, Kohei and Chang, + Gregory and Shim, Hyun Jeong and Chan, Yin and Chen, Shiuan", + abstract = "BACKGROUND: Intratumour heterogeneity is a hallmark of most solid + tumours, including breast cancers. We applied spatial + transcriptomics and single-cell RNA-sequencing on patient-derived + xenografts (PDXs) to profile spatially resolved cell populations + within oestrogen receptor-positive (ER+ ) breast cancer and to + elucidate their importance in oestrogen-dependent tumour growth. + METHODS: Two PDXs of 'ER-high' breast cancers with opposite + oestrogen-mediated growth responses were investigated: + oestrogen-suppressed GS3 (80-100\% ER) and oestrogen-dependent + SC31 (40-90\% ER) models. The observation was validated via + single-cell analyses on an 'ER-low' PDX, GS1 (5\% ER). The + results from our spatial and single-cell analyses were further + supported by a public ER+ breast cancer single-cell dataset and + protein-based dual immunohistochemistry (IHC) of SC31 examining + important luminal cancer markers (i.e., ER, progesterone receptor + and Ki67). The translational implication of our findings was + assessed by clinical outcome analyses on publicly available + cohorts. RESULTS: Our space-gene-function study revealed four + spatially distinct compartments within ER+ breast cancers. These + compartments showed functional diversity (oestrogen-responsive, + proliferative, hypoxia-induced and inflammation-related). The + 'proliferative' population, rather than the + 'oestrogen-responsive' compartment, was crucial for + oestrogen-dependent tumour growth, leading to the acquisition of + luminal B-like features. The cells expressing typical + oestrogen-responsive genes like PGR were not directly linked to + oestrogen-dependent proliferation. Dual IHC analyses demonstrated + the distinct contribution of the Ki67+ proliferative cells toward + oestrogen-mediated growth and their response to a CDK4/6 + inhibitor. The gene signatures derived from the proliferative, + hypoxia-induced and inflammation-related compartments were + significantly correlated with worse clinical outcomes, while + patients with the oestrogen-responsive signature showed better + prognoses, suggesting that this compartment would not be directly + associated with oestrogen-dependent tumour progression. + CONCLUSIONS: Our study identified the gene signature in our + 'proliferative' compartment as an important determinant of + luminal cancer subtypes. This 'proliferative' cell population is + a causative feature of luminal B breast cancer, contributing + toward its aggressive behaviours.", + journal = "Clin. Transl. Med.", + volume = 14, + number = 1, + pages = "e1548", + month = jan, + year = 2024, + keywords = "breast cancer; intratumour heterogeneity; oestrogen receptor; + single-cell RNA-sequencing; spatial transcriptomics", + language = "en" +} + +@ARTICLE{Ballester_Roig2023-hb, + title = "Probing pathways by which rhynchophylline modifies sleep using + spatial transcriptomics", + author = "Ballester Roig, Maria Neus and Leduc, Tanya and Dufort-Gervais, + Julien and Maghmoul, Yousra and Tastet, Olivier and Mongrain, + Val{\'e}rie", + abstract = "BACKGROUND: Rhynchophylline (RHY) is an alkaloid component of + Uncaria, which are plants extensively used in traditional Asian + medicines. Uncaria treatments increase sleep time and quality in + humans, and RHY induces sleep in rats. However, like many + traditional natural treatments, the mechanisms of action of RHY + and Uncaria remain evasive. Moreover, it is unknown whether RHY + modifies key brain oscillations during sleep. We thus aimed at + defining the effects of RHY on sleep architecture and + oscillations throughout a 24-h cycle, as well as identifying the + underlying molecular mechanisms. Mice received systemic RHY + injections at two times of the day (beginning and end of the + light period), and vigilance states were studied by + electrocorticographic recordings. RESULTS: RHY enhanced slow wave + sleep (SWS) after both injections, suppressed paradoxical sleep + (PS) in the light but enhanced PS in the dark period. + Furthermore, RHY modified brain oscillations during both + wakefulness and SWS (including delta activity dynamics) in a + time-dependent manner. Interestingly, most effects were larger in + females. A brain spatial transcriptomic analysis showed that RHY + modifies the expression of genes linked to cell movement, + apoptosis/necrosis, and transcription/translation in a brain + region-independent manner, and changes those linked to sleep + regulation (e.g., Hcrt, Pmch) in a brain region-specific manner + (e.g., in the hypothalamus). CONCLUSIONS: The findings provide + support to the sleep-inducing effect of RHY, expose the relevance + to shape wake/sleep oscillations, and highlight its effects on + the transcriptome with a high spatial resolution. The exposed + molecular mechanisms underlying the effect of a natural compound + should benefit sleep- and brain-related medicine.", + journal = "Biol. Direct", + volume = 18, + number = 1, + pages = "21", + month = may, + year = 2023, + keywords = "Electrocorticographic oscillations; Hypothalamus; Molecular + profiling; Sex; Sleep induction; Slow wave sleep", + language = "en" +} + +% The entry below contains non-ASCII chars that could not be converted +% to a LaTeX equivalent. +@ARTICLE{Villemin2023-ck, + title = "Inferring ligand-receptor cellular networks from bulk and + spatial transcriptomic datasets with {BulkSignalR}", + author = "Villemin, Jean-Philippe and Bassaganyas, Laia and Pourquier, + Didier and Boissi{\`e}re, Florence and Cabello-Aguilar, Simon + and Crapez, Evelyne and Tanos, Rita and Cornillot, Emmanuel and + Turtoi, Andrei and Colinge, Jacques", + abstract = "The study of cellular networks mediated by ligand-receptor + interactions has attracted much attention recently owing to + single-cell omics. However, rich collections of bulk data + accompanied with clinical information exists and continue to be + generated with no equivalent in single-cell so far. In parallel, + spatial transcriptomic (ST) analyses represent a revolutionary + tool in biology. A large number of ST projects rely on + multicellular resolution, for instance the Visium™ platform, + where several cells are analyzed at each location, thus + producing localized bulk data. Here, we describe BulkSignalR, a + R package to infer ligand-receptor networks from bulk data. + BulkSignalR integrates ligand-receptor interactions with + downstream pathways to estimate statistical significance. A + range of visualization methods complement the statistics, + including functions dedicated to spatial data. We demonstrate + BulkSignalR relevance using different datasets, including new + Visium liver metastasis ST data, with experimental validation of + protein colocalization. A comparison with other ST packages + shows the significantly higher quality of BulkSignalR + inferences. BulkSignalR can be applied to any species thanks to + its built-in generic ortholog mapping functionality.", + journal = "Nucleic Acids Res.", + publisher = "Oxford University Press (OUP)", + volume = 51, + number = 10, + pages = "4726--4744", + month = may, + year = 2023, + copyright = "https://creativecommons.org/licenses/by-nc/4.0/", + language = "en" +} + +@ARTICLE{Caronni2023-pe, + title = "{IL-1$\beta$+} macrophages fuel pathogenic inflammation in + pancreatic cancer", + author = "Caronni, Nicoletta and La Terza, Federica and Vittoria, + Francesco M and Barbiera, Giulia and Mezzanzanica, Luca and + Cuzzola, Vincenzo and Barresi, Simona and Pellegatta, Marta and + Canevazzi, Paolo and Dunsmore, Garett and Leonardi, Carlo and + Montaldo, Elisa and Lusito, Eleonora and Dugnani, Erica and + Citro, Antonio and Ng, Melissa S F and Schiavo Lena, Marco and + Drago, Denise and Andolfo, Annapaola and Brugiapaglia, Silvia + and Scagliotti, Alessandro and Mortellaro, Alessandra and Corbo, + Vincenzo and Liu, Zhaoyuan and Mondino, Anna and Dellabona, + Paolo and Piemonti, Lorenzo and Taveggia, Carla and Doglioni, + Claudio and Cappello, Paola and Novelli, Francesco and + Iannacone, Matteo and Ng, Lai Guan and Ginhoux, Florent and + Crippa, Stefano and Falconi, Massimo and Bonini, Chiara and + Naldini, Luigi and Genua, Marco and Ostuni, Renato", + abstract = "Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with + high resistance to therapies1. Inflammatory and immunomodulatory + signals co-exist in the pancreatic tumour microenvironment, + leading to dysregulated repair and cytotoxic responses. + Tumour-associated macrophages (TAMs) have key roles in PDAC2, + but their diversity has prevented therapeutic exploitation. Here + we combined single-cell and spatial genomics with functional + experiments to unravel macrophage functions in pancreatic + cancer. We uncovered an inflammatory loop between tumour cells + and interleukin-1$\beta$ (IL-1$\beta$)-expressing TAMs, a subset + of macrophages elicited by a local synergy between prostaglandin + E2 (PGE2) and tumour necrosis factor (TNF). Physical proximity + with IL-1$\beta$+ TAMs was associated with inflammatory + reprogramming and acquisition of pathogenic properties by a + subset of PDAC cells. This occurrence was an early event in + pancreatic tumorigenesis and led to persistent transcriptional + changes associated with disease progression and poor outcomes + for patients. Blocking PGE2 or IL-1$\beta$ activity elicited TAM + reprogramming and antagonized tumour cell-intrinsic and + -extrinsic inflammation, leading to PDAC control in vivo. + Targeting the PGE2-IL-1$\beta$ axis may enable preventive or + therapeutic strategies for reprogramming of immune dynamics in + pancreatic cancer.", + journal = "Nature", + publisher = "Springer Science and Business Media LLC", + volume = 623, + number = 7986, + pages = "415--422", + month = nov, + year = 2023, + copyright = "https://www.springernature.com/gp/researchers/text-and-data-mining", + language = "en" +} + +@ARTICLE{Sukhanov2023-ja, + title = "Insulin-like growth factor 1 reduces coronary atherosclerosis in + pigs with familial hypercholesterolemia", + author = "Sukhanov, Sergiy and Higashi, Yusuke and Yoshida, Tadashi and + Danchuk, Svitlana and Alfortish, Mitzi and Goodchild, Traci and + Scarborough, Amy and Sharp, Thomas and Jenkins, James S and + Garcia, Daniel and Ivey, Jan and Tharp, Darla L and Schumacher, + Jeffrey and Rozenbaum, Zach and Kolls, Jay K and Bowles, Douglas + and Lefer, David and Delafontaine, Patrice", + abstract = "Although murine models of coronary atherosclerotic disease have + been used extensively to determine mechanisms, limited new + therapeutic options have emerged. Pigs with familial + hypercholesterolemia (FH pigs) develop complex coronary atheromas + that are almost identical to human lesions. We reported + previously that insulin-like growth factor 1 (IGF-1) reduced + aortic atherosclerosis and promoted features of stable plaque in + a murine model. We administered human recombinant IGF-1 or saline + (control) in atherosclerotic FH pigs for 6 months. IGF-1 + decreased relative coronary atheroma in vivo (intravascular + ultrasound) and reduced lesion cross-sectional area (postmortem + histology). IGF-1 increased plaque's fibrous cap thickness, and + reduced necrotic core, macrophage content, and cell apoptosis, + consistent with promotion of a stable plaque phenotype. IGF-1 + reduced circulating triglycerides, markers of systemic oxidative + stress, and CXCL12 chemokine levels. We used spatial + transcriptomics (ST) to identify global transcriptome changes in + advanced plaque compartments and to obtain mechanistic insights + into IGF-1 effects. ST analysis showed that IGF-1 suppressed + FOS/FOSB factors and gene expression of MMP9 and CXCL14 in plaque + macrophages, suggesting possible involvement of these molecules + in IGF-1's effect on atherosclerosis. Thus, IGF-1 reduced + coronary plaque burden and promoted features of stable plaque in + a pig model, providing support for consideration of clinical + trials.", + journal = "JCI Insight", + volume = 8, + number = 4, + month = feb, + year = 2023, + keywords = "Atherosclerosis; Cardiology; Growth factors; Plaque formation; + Vascular Biology", + language = "en" +} + +@ARTICLE{Zhi2024-hz, + title = "Spatial transcriptomic and metabolomic landscapes of oral + submucous fibrosis-derived oral squamous cell carcinoma and its + tumor microenvironment", + author = "Zhi, Yuan and Wang, Qian and Zi, Moxin and Zhang, Shanshan and + Ge, Junshang and Liu, Keyue and Lu, Linsong and Fan, Chunmei and + Yan, Qijia and Shi, Lei and Chen, Pan and Fan, Songqing and Liao, + Qianjin and Guo, Can and Wang, Fuyan and Gong, Zhaojian and + Xiong, Wei and Zeng, Zhaoyang", + abstract = "In South and Southeast Asia, the habit of chewing betel nuts is + prevalent, which leads to oral submucous fibrosis (OSF). OSF is a + well-established precancerous lesion, and a portion of OSF cases + eventually progress to oral squamous cell carcinoma (OSCC). + However, the specific molecular mechanisms underlying the + malignant transformation of OSCC from OSF are poorly understood. + In this study, the leading-edge techniques of Spatial + Transcriptomics (ST) and Spatial Metabolomics (SM) are integrated + to obtain spatial location information of cancer cells, + fibroblasts, and immune cells, as well as the transcriptomic and + metabolomic landscapes in OSF-derived OSCC tissues. This work + reveals for the first time that some OSF-derived OSCC cells + undergo partial epithelial-mesenchymal transition (pEMT) within + the in situ carcinoma (ISC) region, eventually acquiring + fibroblast-like phenotypes and participating in collagen + deposition. Complex interactions among epithelial cells, + fibroblasts, and immune cells in the tumor microenvironment are + demonstrated. Most importantly, significant metabolic + reprogramming in OSF-derived OSCC, including abnormal polyamine + metabolism, potentially playing a pivotal role in promoting + tumorigenesis and immune evasion is discovered. The ST and SM + data in this study shed new light on deciphering the mechanisms + of OSF-derived OSCC. The work also offers invaluable clues for + the prevention and treatment of OSCC.", + journal = "Adv. Sci. (Weinh.)", + volume = 11, + number = 12, + pages = "e2306515", + month = mar, + year = 2024, + keywords = "oral squamous cell carcinoma (OSCC); oral submucous fibrosis + (OSF); polyamine metabolism; spatial metabolomics; spatial + transcriptomics; tumor microenvironment", + language = "en" +} + +@ARTICLE{Kerzel2023-fn, + title = "In vivo macrophage engineering reshapes the tumor + microenvironment leading to eradication of liver metastases", + author = "Kerzel, Thomas and Giacca, Giovanna and Beretta, Stefano and + Bresesti, Chiara and Notaro, Marco and Scotti, Giulia Maria and + Balestrieri, Chiara and Canu, Tamara and Redegalli, Miriam and + Pedica, Federica and Genua, Marco and Ostuni, Renato and + Kajaste-Rudnitski, Anna and Oshima, Masanobu and Tonon, Giovanni + and Merelli, Ivan and Aldrighetti, Luca and Dellabona, Paolo and + Coltella, Nadia and Doglioni, Claudio and Rancoita, Paola M V + and Sanvito, Francesca and Naldini, Luigi and Squadrito, Mario + Leonardo", + abstract = "Liver metastases are associated with poor response to current + pharmacological treatments, including immunotherapy. We describe + a lentiviral vector (LV) platform to selectively engineer liver + macrophages, including Kupffer cells and tumor-associated + macrophages (TAMs), to deliver type I interferon (IFN$\alpha$) + to liver metastases. Gene-based IFN$\alpha$ delivery delays the + growth of colorectal and pancreatic ductal adenocarcinoma liver + metastases in mice. Response to IFN$\alpha$ is associated with + TAM immune activation, enhanced MHC-II-restricted antigen + presentation and reduced exhaustion of CD8+ T cells. Conversely, + increased IL-10 signaling, expansion of Eomes CD4+ T cells, a + cell type displaying features of type I regulatory T (Tr1) + cells, and CTLA-4 expression are associated with resistance to + therapy. Targeting regulatory T cell functions by combinatorial + CTLA-4 immune checkpoint blockade and IFN$\alpha$ LV delivery + expands tumor-reactive T cells, attaining complete response in + most mice. These findings support a promising therapeutic + strategy with feasible translation to patients with unmet + medical need.", + journal = "Cancer Cell", + publisher = "Elsevier BV", + volume = 41, + number = 11, + pages = "1892--1910.e10", + month = nov, + year = 2023, + keywords = "Colorectal cancer (CRC); EOMES; Gene therapy; Immunotherapy; + Interferon-alpha; Interleukin-10 (IL-10); Liver metastases; + Pancreatic cancer; Tumor-associated macrophages (TAMs); Type 1 + regulatory T cells (Tr1)", + copyright = "http://creativecommons.org/licenses/by-nc-nd/4.0/", + language = "en" +} + +@ARTICLE{Mirzazadeh2023-ql, + title = "Spatially resolved transcriptomic profiling of degraded and + challenging fresh frozen samples", + author = "Mirzazadeh, Reza and Andrusivova, Zaneta and Larsson, Ludvig and + Newton, Phillip T and Galicia, Leire Alonso and Abalo, Xes{\'u}s + M and Avijgan, Mahtab and Kvastad, Linda and Denadai-Souza, + Alexandre and Stakenborg, Nathalie and Firsova, Alexandra B and + Shamikh, Alia and Jurek, Aleksandra and Schultz, Niklas and + Nist{\'e}r, Monica and Samakovlis, Christos and Boeckxstaens, + Guy and Lundeberg, Joakim", + abstract = "Spatially resolved transcriptomics has enabled precise + genome-wide mRNA expression profiling within tissue sections. + The performance of methods targeting the polyA tails of mRNA + relies on the availability of specimens with high RNA quality. + Moreover, the high cost of currently available spatial resolved + transcriptomics assays requires a careful sample screening + process to increase the chance of obtaining high-quality data. + Indeed, the upfront analysis of RNA quality can show + considerable variability due to sample handling, storage, and/or + intrinsic factors. We present RNA-Rescue Spatial Transcriptomics + (RRST), a workflow designed to improve mRNA recovery from fresh + frozen specimens with moderate to low RNA quality. First, we + provide a benchmark of RRST against the standard Visium spatial + gene expression protocol on high RNA quality samples represented + by mouse brain and prostate cancer samples. Then, we test the + RRST protocol on tissue sections collected from five challenging + tissue types, including human lung, colon, small intestine, + pediatric brain tumor, and mouse bone/cartilage. In total, we + analyze 52 tissue sections and demonstrate that RRST is a + versatile, powerful, and reproducible protocol for fresh frozen + specimens of different qualities and origins.", + journal = "Nat. Commun.", + publisher = "Springer Science and Business Media LLC", + volume = 14, + number = 1, + pages = "509", + month = jan, + year = 2023, + copyright = "https://creativecommons.org/licenses/by/4.0", + language = "en" +} + +@ARTICLE{Vanrobaeys2023-bw, + title = "Spatial transcriptomics reveals unique gene expression changes + in different brain regions after sleep deprivation", + author = "Vanrobaeys, Yann and Peterson, Zeru J and Walsh, Emily N and + Chatterjee, Snehajyoti and Lin, Li-Chun and Lyons, Lisa C and + Nickl-Jockschat, Thomas and Abel, Ted", + abstract = "Sleep deprivation has far-reaching consequences on the brain and + behavior, impacting memory, attention, and metabolism. Previous + research has focused on gene expression changes in individual + brain regions, such as the hippocampus or cortex. Therefore, it + is unclear how uniformly or heterogeneously sleep loss affects + the brain. Here, we use spatial transcriptomics to define the + impact of a brief period of sleep deprivation across the brain + in male mice. We find that sleep deprivation induced pronounced + differences in gene expression across the brain, with the + greatest changes in the hippocampus, neocortex, hypothalamus, + and thalamus. Both the differentially expressed genes and the + direction of regulation differed markedly across regions. + Importantly, we developed bioinformatic tools to register tissue + sections and gene expression data into a common anatomical + space, allowing a brain-wide comparison of gene expression + patterns between samples. Our results suggest that distinct + molecular mechanisms acting in discrete brain regions underlie + the biological effects of sleep deprivation.", + journal = "Nat. Commun.", + publisher = "Springer Science and Business Media LLC", + volume = 14, + number = 1, + pages = "7095", + month = nov, + year = 2023, + copyright = "https://creativecommons.org/licenses/by/4.0", + language = "en" +} + +@ARTICLE{Liu2023-tk, + title = "Moxibustion improves hypothalamus Aqp4 polarization in {APP/PS1} + mice: Evidence from spatial transcriptomics", + author = "Liu, Shuqing and Li, Hongying and Shen, Yuan and Zhu, Weikang and + Wang, Yong and Wang, Junmeng and Zhang, Ning and Li, Chenyu and + Xie, Lushuang and Wu, Qiaofeng", + abstract = "Aquaporin-4 (AQP4) is highly polarized to perivascular astrocytic + endfeet. Loss of AQP4 polarization is associated with many + diseases. In Alzheimer's disease (AD), AQP4 loses its normal + location and thus reduces the clearance of amyloid-$\beta$ + plaques and tau protein. Clinical and experimental studies showed + that moxibustion can improve the learning and memory abilities of + AD. To explore whether moxibustion can affect the polarization of + AQP4 around the blood-brain barrier (BBB), we used spatial + transcriptomics (ST) to analyze the expression and polarization + of Aqp4 in wild-type mice, APP/PS1 mice, and APP/PS1 mice + intervened by moxibustion. The results showed that moxibustion + improved the loss of abnormal polarization of AQP4 in APP/PS1 + mice, especially in the hypothalamic BBB. Besides, the other 31 + genes with Aqp4 as the core have similar depolarization in + APP/PS1 mice, most of which are also membrane proteins. The + majority of them have been reversed by moxibustion. At the same + time, we employed the cerebrospinal fluid circulation gene set, + which was found to be at a higher level in the group of APP/PS1 + mice with moxibustion treatment. Finally, to further explore its + mechanism, we analyzed the mitochondrial respiratory chain + complex enzymes closely related to energy metabolism and found + that moxibustion can significantly increase the expression of + mitochondrial respiratory chain enzymes such as Cox6a2 in the + hypothalamus, which could provide energy for mRNA transport. Our + research shows that increasing the polarization of hypothalamic + Aqp4 through mitochondrial energy supply may be an important + target for moxibustion to improve cognitive impairment in APP/PS1 + mice.", + journal = "Front. Aging Neurosci.", + volume = 15, + pages = "1069155", + month = feb, + year = 2023, + keywords = "Alzheimer's disease; aquaporin-4; hypothalamus; mitochondrial + respiratory chain; moxibustion; spatial transcriptomics", + language = "en" +} + +@ARTICLE{Chaker2023-cj, + title = "Pregnancy-responsive pools of adult neural stem cells for + transient neurogenesis in mothers", + author = "Chaker, Zayna and Segalada, Corina and Kretz, Jonas A and Acar, + Ilhan E and Delgado, Ana C and Crotet, Valerie and Moor, Andreas + E and Doetsch, Fiona", + abstract = "Adult neural stem cells (NSCs) contribute to lifelong brain + plasticity. In the adult mouse ventricular-subventricular zone, + NSCs are heterogeneous and, depending on their location in the + niche, give rise to different subtypes of olfactory bulb (OB) + interneurons. Here, we show that multiple regionally distinct + NSCs, including domains that are usually quiescent, are recruited + on different gestation days during pregnancy. Synchronized + activation of these adult NSC pools generates transient waves of + short-lived OB interneurons, especially in layers with less + neurogenesis under homeostasis. Using spatial transcriptomics, we + identified molecular markers of pregnancy-associated interneurons + and showed that some subsets are temporarily needed for own pup + recognition. Thus, pregnancy triggers transient yet behaviorally + relevant neurogenesis, highlighting the physiological relevance + of adult stem cell heterogeneity.", + journal = "Science", + volume = 382, + number = 6673, + pages = "958--963", + month = nov, + year = 2023, + language = "en" +} + +@ARTICLE{Deshpande2023-eo, + title = "Uncovering the spatial landscape of molecular interactions + within the tumor microenvironment through latent spaces", + author = "Deshpande, Atul and Loth, Melanie and Sidiropoulos, Dimitrios N + and Zhang, Shuming and Yuan, Long and Bell, Alexander T F and + Zhu, Qingfeng and Ho, Won Jin and Santa-Maria, Cesar and Gilkes, + Daniele M and Williams, Stephen R and Uytingco, Cedric R and + Chew, Jennifer and Hartnett, Andrej and Bent, Zachary W and + Favorov, Alexander V and Popel, Aleksander S and Yarchoan, Mark + and Kiemen, Ashley and Wu, Pei-Hsun and Fujikura, Kohei and + Wirtz, Denis and Wood, Laura D and Zheng, Lei and Jaffee, + Elizabeth M and Anders, Robert A and Danilova, Ludmila and + Stein-O'Brien, Genevieve and Kagohara, Luciane T and Fertig, + Elana J", + abstract = "Recent advances in spatial transcriptomics (STs) enable gene + expression measurements from a tissue sample while retaining its + spatial context. This technology enables unprecedented in situ + resolution of the regulatory pathways that underlie the + heterogeneity in the tumor as well as the tumor microenvironment + (TME). The direct characterization of cellular co-localization + with spatial technologies facilities quantification of the + molecular changes resulting from direct cell-cell interaction, + as it occurs in tumor-immune interactions. We present + SpaceMarkers, a bioinformatics algorithm to infer molecular + changes from cell-cell interactions from latent space analysis + of ST data. We apply this approach to infer the molecular + changes from tumor-immune interactions in Visium spatial + transcriptomics data of metastasis, invasive and precursor + lesions, and immunotherapy treatment. Further transfer learning + in matched scRNA-seq data enabled further quantification of the + specific cell types in which SpaceMarkers are enriched. + Altogether, SpaceMarkers can identify the location and + context-specific molecular interactions within the TME from ST + data.", + journal = "Cell Syst.", + publisher = "Elsevier BV", + volume = 14, + number = 4, + pages = "285--301.e4", + month = apr, + year = 2023, + keywords = "cell-cell interactions; latent space factorization; single-cell + transcriptomics; spatial analysis; spatial transcriptomics; + transfer learning; tumor microenvironment", + language = "en" +} + +@ARTICLE{Deshpande2023-bt, + title = "Uncovering the spatial landscape of molecular interactions within + the tumor microenvironment through latent spaces", + author = "Deshpande, Atul and Loth, Melanie and Sidiropoulos, Dimitrios N + and Zhang, Shuming and Yuan, Long and Bell, Alexander T F and + Zhu, Qingfeng and Ho, Won Jin and Santa-Maria, Cesar and Gilkes, + Daniele M and Williams, Stephen R and Uytingco, Cedric R and + Chew, Jennifer and Hartnett, Andrej and Bent, Zachary W and + Favorov, Alexander V and Popel, Aleksander S and Yarchoan, Mark + and Kiemen, Ashley and Wu, Pei-Hsun and Fujikura, Kohei and + Wirtz, Denis and Wood, Laura D and Zheng, Lei and Jaffee, + Elizabeth M and Anders, Robert A and Danilova, Ludmila and + Stein-O'Brien, Genevieve and Kagohara, Luciane T and Fertig, + Elana J", + journal = "Cell Syst.", + volume = 14, + number = 8, + pages = "722", + month = aug, + year = 2023, + language = "en" +} + +@ARTICLE{Stec2023-md, + title = "A cellular and molecular spatial atlas of dystrophic muscle", + author = "Stec, Michael J and Su, Qi and Adler, Christina and Zhang, Lance + and Golann, David R and Khan, Naveen P and Panagis, Lampros and + Villalta, S Armando and Ni, Min and Wei, Yi and Walls, Johnathon + R and Murphy, Andrew J and Yancopoulos, George D and Atwal, + Gurinder S and Kleiner, Sandra and Halasz, Gabor and Sleeman, + Mark W", + abstract = "Asynchronous skeletal muscle degeneration/regeneration is a + hallmark feature of Duchenne muscular dystrophy (DMD); however, + traditional -omics technologies that lack spatial context make it + difficult to study the biological mechanisms of how asynchronous + regeneration contributes to disease progression. Here, using the + severely dystrophic D2-mdx mouse model, we generated a + high-resolution cellular and molecular spatial atlas of + dystrophic muscle by integrating spatial transcriptomics and + single-cell RNAseq datasets. Unbiased clustering revealed + nonuniform distribution of unique cell populations throughout + D2-mdx muscle that were associated with multiple regenerative + timepoints, demonstrating that this model faithfully + recapitulates the asynchronous regeneration observed in human DMD + muscle. By probing spatiotemporal gene expression signatures, we + found that propagation of inflammatory and fibrotic signals from + locally damaged areas contributes to widespread pathology and + that querying expression signatures within discrete + microenvironments can identify targetable pathways for DMD + therapy. Overall, this spatial atlas of dystrophic muscle + provides a valuable resource for studying DMD disease biology and + therapeutic target discovery.", + journal = "Proc. Natl. Acad. Sci. U. S. A.", + volume = 120, + number = 29, + pages = "e2221249120", + month = jul, + year = 2023, + keywords = "Duchenne muscular dystrophy; asynchronous regeneration; skeletal + muscle; spatial transcriptomics", + language = "en" +} + +@ARTICLE{Chitturi2023-tv, + title = "Tripterygium wilfordii derivative celastrol, a {YAP} inhibitor, + has antifibrotic effects in systemic sclerosis", + author = "Chitturi, Pratyusha and Xu, Shiwen and Ahmed Abdi, Bahja and + Nguyen, John and Carter, David E and Sinha, Sartak and Arora, + Rohit and Biernaskie, Jeff and Stratton, Richard J and Leask, + Andrew", + abstract = "OBJECTIVES: Systemic sclerosis (SSc) is characterised by + extensive tissue fibrosis maintained by + mechanotranductive/proadhesive signalling. Drugs targeting this + pathway are therefore of likely therapeutic benefit. The + mechanosensitive transcriptional co-activator, yes activated + protein-1 (YAP1), is activated in SSc fibroblasts. The terpenoid + celastrol is a YAP1 inhibitor; however, if celastrol can + alleviate SSc fibrosis is unknown. Moreover, the cell niches + required for skin fibrosis are unknown. METHODS: Human dermal + fibroblasts from healthy individuals and patients with diffuse + cutaneous SSc were treated with or without transforming growth + factor $\beta$1 (TGF$\beta$1), with or without celastrol. Mice + were subjected to the bleomycin-induced model of skin SSc, in the + presence or absence of celastrol. Fibrosis was assessed using RNA + Sequencing, real-time PCR, spatial transcriptomic analyses, + Western blot, ELISA and histological analyses. RESULTS: In dermal + fibroblasts, celastrol impaired the ability of TGF$\beta$1 to + induce an SSc-like pattern of gene expression, including that of + cellular communication network factor 2, collagen I and + TGF$\beta$1. Celastrol alleviated the persistent fibrotic + phenotype of dermal fibroblasts cultured from lesions of SSc + patients. In the bleomycin-induced model of skin SSc, increased + expression of genes associated with reticular fibroblast and + hippo/YAP clusters was observed; conversely, celastrol inhibited + these bleomycin-induced changes and blocked nuclear localisation + of YAP. CONCLUSIONS: Our data clarify niches within the skin + activated in fibrosis and suggest that compounds, such as + celastrol, that antagonise the YAP pathway may be potential + treatments for SSc skin fibrosis.", + journal = "Ann. Rheum. Dis.", + volume = 82, + number = 9, + pages = "1191--1204", + month = sep, + year = 2023, + keywords = "Arthritis, Experimental; Fibroblasts; Scleroderma, Systemic; + Therapeutics", + language = "en" +} + +@ARTICLE{Pavel2023-ip, + title = "Comparison of the Illumina {NextSeq} 2000 and {GeneMind} Genolab + {M} sequencing platforms for spatial transcriptomics", + author = "Pavel, Iamshchikov and Irina, Larionova and Tatiana, Gerashchenko + and Denis, Piankov and Philipp, Koshkin and Sergei, Korostelev + and Evgeny, Denisov", + abstract = "BACKGROUND: The Illumina sequencing systems demonstrate high + efficiency and power and remain the most popular platforms. + Platforms with similar throughput and quality profiles but lower + costs are under intensive development. In this study, we compared + two platforms Illumina NextSeq 2000 and GeneMind Genolab M for + 10x Genomics Visium spatial transcriptomics. RESULTS: The + performed comparison demonstrates that GeneMind Genolab M + sequencing platform produces highly consistent with Illumina + NextSeq 2000 sequencing results. Both platforms have similar + performance in terms of sequencing quality and detection of UMI, + spatial barcode, and probe sequence. Raw read mapping and + following read counting produced highly comparable results that + is confirmed by quality control metrics and strong correlation + between expression profiles in the same tissue spots. Downstream + analysis including dimension reduction and clustering + demonstrated similar results, and differential gene expression + analysis predominantly detected the same genes for both + platforms. CONCLUSIONS: GeneMind Genolab M instrument is similar + to Illumina sequencing efficacy and is suitable for 10x Genomics + Visium spatial transcriptomics.", + journal = "BMC Genomics", + volume = 24, + number = 1, + pages = "102", + month = mar, + year = 2023, + keywords = "10x Genomics Visium; GeneMind Genolab M; Illumina NextSeq 2000; + Sequencing; Spatial transcriptomics", + language = "en" +} + +@ARTICLE{Wu2024-oi, + title = "High resolution spatial profiling of kidney injury and repair + using {RNA} hybridization-based in situ sequencing", + author = "Wu, Haojia and Dixon, Eryn E and Xuanyuan, Qiao and Guo, Juanru + and Yoshimura, Yasuhiro and Debashish, Chitnis and Niesnerova, + Anezka and Xu, Hao and Rouault, Morgane and Humphreys, Benjamin + D", + abstract = "Emerging spatially resolved transcriptomics technologies allow + for the measurement of gene expression in situ at cellular + resolution. We apply direct RNA hybridization-based in situ + sequencing (dRNA HybISS, Cartana part of 10xGenomics) to compare + male and female healthy mouse kidneys and the male kidney injury + and repair timecourse. A pre-selected panel of 200 genes is used + to identify cell state dynamics patterns during injury and + repair. We develop a new computational pipeline, CellScopes, for + the rapid analysis, multi-omic integration and visualization of + spatially resolved transcriptomic datasets. The resulting + dataset allows us to resolve 13 kidney cell types within + distinct kidney niches, dynamic alterations in cell state over + the course of injury and repair and cell-cell interactions + between leukocytes and kidney parenchyma. At late timepoints + after injury, C3+ leukocytes are enriched near pro-inflammatory, + failed-repair proximal tubule cells. Integration of snRNA-seq + dataset from the same injury and repair samples also allows us + to impute the spatial localization of genes not directly + measured by dRNA HybISS.", + journal = "Nat. Commun.", + publisher = "Springer Science and Business Media LLC", + volume = 15, + number = 1, + pages = "1396", + month = feb, + year = 2024, + copyright = "https://creativecommons.org/licenses/by/4.0", + language = "en" +} + +@ARTICLE{Moeyersoms2023-it, + title = "Spatial transcriptomics identifies expression signatures specific + to lacrimal gland adenoid cystic carcinoma cells", + author = "Moeyersoms, Acadia H M and Gallo, Ryan A and Zhang, Michelle G + and Stathias, Vasileios and Maeng, Michelle M and Owens, Dawn and + Abou Khzam, Rayan and Sayegh, Yoseph and Maza, Cynthia and + Dubovy, Sander R and Tse, David T and Pelaez, Daniel", + abstract = "Although primary tumors of the lacrimal gland are rare, adenoid + cystic carcinoma (ACC) is the most common and lethal epithelial + lacrimal gland malignancy. Traditional management of lacrimal + gland adenoid cystic carcinoma (LGACC) involves the removal of + the eye and surrounding socket contents, followed by + chemoradiation. Even with this radical treatment, the 10-year + survival rate for LGACC is 20\% given the propensity for + recurrence and metastasis. Due to the rarity of LGACC, its + pathobiology is not well-understood, leading to difficulties in + diagnosis, treatment, and effective management. Here, we + integrate bulk RNA sequencing (RNA-seq) and spatial + transcriptomics to identify a specific LGACC gene signature that + can inform novel targeted therapies. Of the 3499 differentially + expressed genes identified by bulk RNA-seq, the results of our + spatial transcriptomic analysis reveal 15 upregulated and 12 + downregulated genes that specifically arise from LGACC cells, + whereas fibroblasts, reactive fibrotic tissue, and nervous and + skeletal muscle account for the remaining bulk RNA-seq signature. + In light of the analysis, we identified a transitional state cell + or stem cell cluster. The results of the pathway analysis + identified the upregulation of PI3K-Akt signaling, IL-17 + signaling, and multiple other cancer pathways. This study + provides insights into the molecular and cellular landscape of + LGACC, which can inform new, targeted therapies to improve + patient outcomes.", + journal = "Cancers (Basel)", + volume = 15, + number = 12, + month = jun, + year = 2023, + keywords = "lacrimal gland adenoid cystic carcinoma; rare cancer; spatial + transcriptomics; transcriptomic signature", + language = "en" +} + +@ARTICLE{Rauber2024-kd, + title = "{CD200+} fibroblasts form a pro-resolving mesenchymal network in + arthritis", + author = "Rauber, Simon and Mohammadian, Hashem and Schmidkonz, Christian + and Atzinger, Armin and Soare, Alina and Treutlein, Christoph and + Kemble, Samuel and Mahony, Christopher B and Geisthoff, Manuel + and Angeli, Mario R and Raimondo, Maria G and Xu, Cong and Yang, + Kai-Ting and Lu, Le and Labinsky, Hannah and Saad, Mina S A and + Gwellem, Charles A and Chang, Jiyang and Huang, Kaiyue and + Kampylafka, Eleni and Knitza, Johannes and Bilyy, Rostyslav and + Distler, J{\"o}rg H W and Hanlon, Megan M and Fearon, Ursula and + Veale, Douglas J and Roemer, Frank W and B{\"a}uerle, Tobias and + Maric, Hans M and Maschauer, Simone and Ekici, Arif B and + Buckley, Christopher D and Croft, Adam P and Kuwert, Torsten and + Prante, Olaf and Ca{\~n}ete, Juan D and Schett, Georg and + Ramming, Andreas", + abstract = "Fibroblasts are important regulators of inflammation, but whether + fibroblasts change phenotype during resolution of inflammation is + not clear. Here we use positron emission tomography to detect + fibroblast activation protein (FAP) as a means to visualize + fibroblast activation in vivo during inflammation in humans. + While tracer accumulation is high in active arthritis, it + decreases after tumor necrosis factor and interleukin-17A + inhibition. Biopsy-based single-cell RNA-sequencing analyses in + experimental arthritis show that FAP signal reduction reflects a + phenotypic switch from pro-inflammatory MMP3+/IL6+ fibroblasts + (high FAP internalization) to pro-resolving CD200+DKK3+ + fibroblasts (low FAP internalization). Spatial transcriptomics of + human joints indicates that pro-resolving niches of CD200+DKK3+ + fibroblasts cluster with type 2 innate lymphoid cells, whereas + MMP3+/IL6+ fibroblasts colocalize with inflammatory immune cells. + CD200+DKK3+ fibroblasts stabilized the type 2 innate lymphoid + cell phenotype and induced resolution of arthritis via + CD200-CD200R1 signaling. Taken together, these data suggest a + dynamic molecular regulation of the mesenchymal compartment + during resolution of inflammation.", + journal = "Nat. Immunol.", + volume = 25, + number = 4, + pages = "682--692", + month = apr, + year = 2024, + language = "en" +} + +@ARTICLE{Sans2023-ny, + title = "Spatial transcriptomics of intraductal papillary mucinous + neoplasms of the pancreas identifies {NKX6-2} as a driver of + gastric differentiation and indolent biological potential", + author = "Sans, Marta and Makino, Yuki and Min, Jimin and Rajapakshe, Kimal + I and Yip-Schneider, Michele and Schmidt, C Max and Hurd, Mark W + and Burks, Jared K and Gomez, Javier A and Thege, Fredrik I and + Fahrmann, Johannes F and Wolff, Robert A and Kim, Michael P and + Guerrero, Paola A and Maitra, Anirban", + abstract = "Intraductal papillary mucinous neoplasms (IPMN) of the pancreas + are bona fide precursor lesions of pancreatic ductal + adenocarcinoma (PDAC). The most common subtype of IPMNs harbors a + gastric foveolar-type epithelium, and these low-grade mucinous + neoplasms are harbingers of IPMNs with high-grade dysplasia and + cancer. The molecular underpinning of gastric differentiation in + IPMNs is unknown, although identifying drivers of this indolent + phenotype might enable opportunities for intercepting progression + to high-grade IPMN and cancer. We conducted spatial + transcriptomics on a cohort of IPMNs, followed by orthogonal and + cross-species validation studies, which established the + transcription factor NKX6-2 as a key determinant of gastric cell + identity in low-grade IPMNs. Loss of NKX6-2 expression is a + consistent feature of IPMN progression, while reexpression of + Nkx6-2 in murine IPMN lines recapitulates the aforementioned + gastric transcriptional program and glandular morphology. Our + study identifies NKX6-2 as a previously unknown transcription + factor driving indolent gastric differentiation in IPMN + pathogenesis. SIGNIFICANCE: Identification of the molecular + features driving IPMN development and differentiation is critical + to prevent cancer progression and enhance risk stratification. We + used spatial profiling to characterize the epithelium and + microenvironment of IPMN, which revealed a previously unknown + link between NKX6-2 and gastric differentiation, the latter + associated with indolent biological potential. See related + commentary by Ben-Shmuel and Scherz-Shouval, p. 1768. This + article is highlighted in the In This Issue feature, p. 1749.", + journal = "Cancer Discov.", + volume = 13, + number = 8, + pages = "1844--1861", + month = aug, + year = 2023, + language = "en" +} + +@ARTICLE{Gharaie2023-mn, + title = "Single cell and spatial transcriptomics analysis of kidney double + negative {T} lymphocytes in normal and ischemic mouse kidneys", + author = "Gharaie, Sepideh and Lee, Kyungho and Noller, Kathleen and Lo, + Emily K and Miller, Brendan and Jung, Hyun Jun and Newman-Rivera, + Andrea M and Kurzhagen, Johanna T and Singla, Nirmish and + Welling, Paul A and Fan, Jean and Cahan, Patrick and Noel, + Sanjeev and Rabb, Hamid", + abstract = "T cells are important in the pathogenesis of acute kidney injury + (AKI), and TCR+CD4-CD8- (double negative-DN) are T cells that + have regulatory properties. However, there is limited information + on DN T cells compared to traditional CD4+ and CD8+ cells. To + elucidate the molecular signature and spatial dynamics of DN T + cells during AKI, we performed single-cell RNA sequencing + (scRNA-seq) on sorted murine DN, CD4+, and CD8+ cells combined + with spatial transcriptomic profiling of normal and post AKI + mouse kidneys. scRNA-seq revealed distinct transcriptional + profiles for DN, CD4+, and CD8+ T cells of mouse kidneys with + enrichment of Kcnq5, Klrb1c, Fcer1g, and Klre1 expression in DN T + cells compared to CD4+ and CD8+ T cells in normal kidney tissue. + We validated the expression of these four genes in mouse kidney + DN, CD4+ and CD8+ T cells using RT-PCR and Kcnq5, Klrb1, and + Fcer1g genes with the NIH human kidney precision medicine project + (KPMP). Spatial transcriptomics in normal and ischemic mouse + kidney tissue showed a localized cluster of T cells in the outer + medulla expressing DN T cell genes including Fcer1g. These + results provide a template for future studies in DN T as well as + CD4+ and CD8+ cells in normal and diseased kidneys.", + journal = "Sci. Rep.", + volume = 13, + number = 1, + pages = "20888", + month = nov, + year = 2023, + language = "en" +} + +@ARTICLE{Mei2023-fx, + title = "Siglec-9 acts as an immune-checkpoint molecule on macrophages in + glioblastoma, restricting T-cell priming and immunotherapy + response", + author = "Mei, Yan and Wang, Xiumei and Zhang, Ji and Liu, Dan and He, + Junjie and Huang, Chunliu and Liao, Jing and Wang, Yingzhao and + Feng, Yongyi and Li, Hongyu and Liu, Xiuying and Chen, Lingdan + and Yi, Wei and Chen, Xi and Bai, Hong-Min and Wang, Xinyu and + Li, Yiyi and Wang, Lixiang and Liang, Zhigang and Ren, Xianwen + and Qiu, Li and Hui, Yuan and Zhang, Qingling and Leng, Qibin + and Chen, Jun and Jia, Guangshuai", + abstract = "Neoadjuvant immune-checkpoint blockade therapy only benefits a + limited fraction of patients with glioblastoma multiforme (GBM). + Thus, targeting other immunomodulators on myeloid cells is an + attractive therapeutic option. Here, we performed single-cell + RNA sequencing and spatial transcriptomics of patients with GBM + treated with neoadjuvant anti-PD-1 therapy. We identified unique + monocyte-derived tumor-associated macrophage subpopulations with + functional plasticity that highly expressed the + immunosuppressive SIGLEC9 gene and preferentially accumulated in + the nonresponders to anti-PD-1 treatment. Deletion of Siglece + (murine homolog) resulted in dramatically restrained tumor + development and prolonged survival in mouse models. + Mechanistically, targeting Siglece directly activated both CD4+ + T cells and CD8+ T cells through antigen presentation, secreted + chemokines and co-stimulatory factor interactions. Furthermore, + Siglece deletion synergized with anti-PD-1/PD-L1 treatment to + improve antitumor efficacy. Our data demonstrated that Siglec-9 + is an immune-checkpoint molecule on macrophages that can be + targeted to enhance anti-PD-1/PD-L1 therapeutic efficacy for GBM + treatment.", + journal = "Nat. Cancer", + publisher = "Springer Science and Business Media LLC", + volume = 4, + number = 9, + pages = "1273--1291", + month = sep, + year = 2023, + copyright = "https://www.springernature.com/gp/researchers/text-and-data-mining", + language = "en" +} + +@ARTICLE{Nakata2023-sb, + title = "Genetic vulnerability to Crohn's disease reveals a spatially + resolved epithelial restitution program", + author = "Nakata, Toru and Li, Chenhao and Mayassi, Toufic and Lin, Helen + and Ghosh, Koushik and Segerstolpe, {\AA}sa and Diamond, Emma L + and Herbst, Paula and Biancalani, Tommaso and Gaddam, Shreya and + Parkar, Saurabh and Lu, Ziqing and Jaiswal, Alok and Li, Bihua + and Creasey, Elizabeth A and Lefkovith, Ariel and Daly, Mark J + and Graham, Daniel B and Xavier, Ramnik J", + abstract = "Effective tissue repair requires coordinated intercellular + communication to sense damage, remodel the tissue, and restore + function. Here, we dissected the healing response in the + intestinal mucosa by mapping intercellular communication at + single-cell resolution and integrating with spatial + transcriptomics. We demonstrated that a risk variant for Crohn's + disease, hepatocyte growth factor activator (HGFAC) Arg509His + (R509H), disrupted a damage-sensing pathway connecting the + coagulation cascade to growth factors that drive the + differentiation of wound-associated epithelial (WAE) cells and + production of a localized retinoic acid (RA) gradient to promote + fibroblast-mediated tissue remodeling. Specifically, we showed + that HGFAC R509H was activated by thrombin protease activity but + exhibited impaired proteolytic activation of the growth factor + macrophage-stimulating protein (MSP). In Hgfac R509H mice, + reduced MSP activation in response to wounding of the colon + resulted in impaired WAE cell induction and delayed healing. + Through integration of single-cell transcriptomics and spatial + transcriptomics, we demonstrated that WAE cells generated RA in + a spatially restricted region of the wound site and that mucosal + fibroblasts responded to this signal by producing extracellular + matrix and growth factors. We further dissected this WAE + cell-fibroblast signaling circuit in vitro using a genetically + tractable organoid coculture model. Collectively, these studies + exploited a genetic perturbation associated with human disease + to disrupt a fundamental biological process and then + reconstructed a spatially resolved mechanistic model of tissue + healing.", + journal = "Sci. Transl. Med.", + publisher = "American Association for the Advancement of Science (AAAS)", + volume = 15, + number = 719, + pages = "eadg5252", + month = oct, + year = 2023, + language = "en" +} + +@ARTICLE{Pham2023-ey, + title = "Robust mapping of spatiotemporal trajectories and cell-cell + interactions in healthy and diseased tissues", + author = "Pham, Duy and Tan, Xiao and Balderson, Brad and Xu, Jun and + Grice, Laura F and Yoon, Sohye and Willis, Emily F and Tran, Minh + and Lam, Pui Yeng and Raghubar, Arti and Kalita-de Croft, + Priyakshi and Lakhani, Sunil and Vukovic, Jana and Ruitenberg, + Marc J and Nguyen, Quan H", + abstract = "Spatial transcriptomics (ST) technologies generate multiple data + types from biological samples, namely gene expression, physical + distance between data points, and/or tissue morphology. Here we + developed three computational-statistical algorithms that + integrate all three data types to advance understanding of + cellular processes. First, we present a spatial graph-based + method, pseudo-time-space (PSTS), to model and uncover + relationships between transcriptional states of cells across + tissues undergoing dynamic change (e.g. neurodevelopment, brain + injury and/or microglia activation, and cancer progression). We + further developed a spatially-constrained two-level permutation + (SCTP) test to study cell-cell interaction, finding highly + interactive tissue regions across thousands of ligand-receptor + pairs with markedly reduced false discovery rates. Finally, we + present a spatial graph-based imputation method with neural + network (stSME), to correct for technical noise/dropout and + increase ST data coverage. Together, the algorithms that we + developed, implemented in the comprehensive and fast stLearn + software, allow for robust interrogation of biological processes + within healthy and diseased tissues.", + journal = "Nat. Commun.", + volume = 14, + number = 1, + pages = "7739", + month = nov, + year = 2023, + language = "en" +} + +@ARTICLE{Andrews2024-eh, + title = "Single-cell, single-nucleus, and spatial transcriptomics + characterization of the immunological landscape in the healthy + and {PSC} human liver", + author = "Andrews, Tallulah S and Nakib, Diana and Perciani, Catia T and + Ma, Xue Zhong and Liu, Lewis and Winter, Erin and Camat, Damra + and Chung, Sai W and Lumanto, Patricia and Manuel, Justin and + Mangroo, Shantel and Hansen, Bettina and Arpinder, Bal and + Thoeni, Cornelia and Sayed, Blayne and Feld, Jordan and Gehring, + Adam and Gulamhusein, Aliya and Hirschfield, Gideon M and + Ricciuto, Amanda and Bader, Gary D and McGilvray, Ian D and + MacParland, Sonya", + abstract = "BACKGROUND \& AIMS: Primary sclerosing cholangitis (PSC) is an + immune-mediated cholestatic liver disease for which there is an + unmet need to understand the cellular composition of the affected + liver and how it underlies disease pathogenesis. We aimed to + generate a comprehensive atlas of the PSC liver using multi-omic + modalities and protein-based functional validation. METHODS: We + employed single-cell and single-nucleus RNA sequencing (47,156 + cells and 23,000 nuclei) and spatial transcriptomics (one sample + by 10x Visium and five samples with Nanostring GeoMx DSP) to + profile the cellular ecosystem in 10 PSC livers. Transcriptomic + profiles were compared to 24 neurologically deceased donor livers + (107,542 cells) and spatial transcriptomics controls, as well as + 18,240 cells and 20,202 nuclei from three PBC livers. Flow + cytometry was performed to validate PSC-specific differences in + immune cell phenotype and function. RESULTS: PSC explants with + parenchymal cirrhosis and prominent periductal fibrosis contained + a population of cholangiocyte-like hepatocytes that were + surrounded by diverse immune cell populations. PSC-associated + biliary, mesenchymal, and endothelial populations expressed + chemokine and cytokine transcripts involved in immune cell + recruitment. Additionally, expanded CD4+ T cells and recruited + myeloid populations in the PSC liver expressed the corresponding + receptors to these chemokines and cytokines, suggesting potential + recruitment. Tissue-resident macrophages, by contrast, were + reduced in number and exhibited a dysfunctional and downregulated + inflammatory response to lipopolysaccharide and + interferon-$\gamma$ stimulation. CONCLUSIONS: We present a + comprehensive atlas of the PSC liver and demonstrate an + exhaustion-like phenotype of myeloid cells and markers of chronic + cytokine expression in late-stage PSC lesions. This atlas expands + our understanding of the cellular complexity of PSC and has + potential to guide the development of novel treatments. IMPACT + AND IMPLICATIONS: Primary sclerosing cholangitis (PSC) is a rare + liver disease characterized by chronic inflammation and + irreparable damage to the bile ducts, which eventually results in + liver failure. Due to a limited understanding of the underlying + pathogenesis of disease, treatment options are limited. To + address this, we sequenced healthy and diseased livers to compare + the activity, interactions, and localization of immune and + non-immune cells. This revealed that hepatocytes lining PSC scar + regions co-express cholangiocyte markers, whereas immune cells + infiltrate the scar lesions. Of these cells, macrophages, which + typically contribute to tissue repair, were enriched in + immunoregulatory genes and demonstrated a lack of responsiveness + to stimulation. These cells may be involved in maintaining + hepatic inflammation and could be a target for novel therapies.", + journal = "J. Hepatol.", + month = jan, + year = 2024, + keywords = "Liver; Myeloid Dysfunction; Primary Sclerosing Cholangitis; + Single Cell RNA sequencing; Spatial Transcriptomics", + language = "en" +} + +@ARTICLE{Di_Marco2023-jg, + title = "Spatial transcriptomics map of the embryonic mouse brain - a tool + to explore neurogenesis", + author = "Di Marco, Barbara and V{\'a}zquez-Mar{\'\i}n, Javier and Monyer, + Hannah and Centanin, L{\'a}zaro and Alfonso, Julieta", + abstract = "The developing brain has a well-organized anatomical structure + comprising different types of neural and non-neural cells. Stem + cells, progenitors and newborn neurons tightly interact with + their neighbouring cells and tissue microenvironment, and this + intricate interplay ultimately shapes the output of neurogenesis. + Given the relevance of spatial cues during brain development, we + acknowledge the necessity for a spatial transcriptomics map + accessible to the neurodevelopmental community. To fulfil this + need, we generated spatially resolved RNA sequencing (RNAseq) + data from embryonic day 13.5 mouse brain sections immunostained + for mitotic active neural and vascular cells. Unsupervised + clustering defined specific cell type populations of diverse + lineages and differentiation states. Differential expression + analysis revealed unique transcriptional signatures across + specific brain areas, uncovering novel features inherent to + particular anatomical domains. Finally, we integrated existing + single-cell RNAseq datasets into our spatial transcriptomics map, + adding tissue context to single-cell RNAseq data. In summary, we + provide a valuable tool that enables the exploration and + discovery of unforeseen molecular players involved in + neurogenesis, particularly in the crosstalk between different + cell types.", + journal = "Biol. Open", + volume = 12, + number = 10, + month = oct, + year = 2023, + keywords = "Gene expression atlas; Mouse telencephalon; Neurodevelopment; + Single-cell and spatial transcriptomics data integration", + language = "en" +} + +@ARTICLE{Kawai2023-en, + title = "Clonal proliferation within smooth muscle cells in unstable + human atherosclerotic lesions", + author = "Kawai, Kenji and Sakamoto, Atsushi and Mokry, Michal and Ghosh, + Saikat Kumar B and Kawakami, Rika and Xu, Weili and Guo, Liang + and Fuller, Daniela T and Tanaka, Takamasa and Shah, Palak and + Cornelissen, Anne and Sato, Yu and Mori, Masayuki and Konishi, + Takao and Vozenilek, Aimee E and Dhingra, Roma and Virmani, Renu + and Pasterkamp, Gerard and Finn, Aloke V", + abstract = "BACKGROUND: Studies in humans and mice using the expression of + an X-linked gene or lineage tracing, respectively, have + suggested that clones of smooth muscle cells (SMCs) exist in + human atherosclerotic lesions but are limited by either spatial + resolution or translatability of the model. METHODS: Phenotypic + clonality can be detected by X-chromosome inactivation patterns. + We investigated whether clones of SMCs exist in unstable human + atheroma using RNA in situ hybridization (BaseScope) to identify + a naturally occurring 24-nucleotide deletion in the 3'UTR of the + X-linked BGN (biglycan) gene, a proteoglycan highly expressed by + SMCs. BGN-specific BaseScope probes were designed to target the + wild-type or deletion mRNA. Three different coronary artery + plaque types (erosion, rupture, and adaptive intimal thickening) + were selected from heterozygous females for the deletion BGN. + Hybridization of target RNA-specific probes was used to + visualize the spatial distribution of mutants. A clonality index + was calculated from the percentage of each probe in each region + of interest. Spatial transcriptomics were used to identify + differentially expressed transcripts within clonal and nonclonal + regions. RESULTS: Less than one-half of regions of interest in + the intimal plaque were considered clonal with the mean percent + regions of interest with clonality higher in the intimal plaque + than in the media. This was consistent for all plaque types. The + relationship of the dominant clone in the intimal plaque and + media showed significant concordance. In comparison with the + nonclonal lesions, the regions with SMC clonality had lower + expression of genes encoding cell growth suppressors such as + CD74, SERF-2 (small EDRK-rich factor 2), CTSB (cathepsin B), and + HLA-DPA1 (major histocompatibility complex, class II, DP alpha + 1), among others. CONCLUSIONS: Our novel approach to examine + clonality suggests atherosclerosis is primarily a disease of + polyclonally and to a lesser extent clonally expanded SMCs and + may have implications for the development of antiatherosclerotic + therapies.", + journal = "Arterioscler. Thromb. Vasc. Biol.", + publisher = "Ovid Technologies (Wolters Kluwer Health)", + volume = 43, + number = 12, + pages = "2333--2347", + month = dec, + year = 2023, + keywords = "atherosclerosis; biglycan; coronary artery disease; gene + expression; pathology", + language = "en" +} + +@ARTICLE{Zhong2023-zy, + title = "Multi-species atlas resolves an axolotl limb development and + regeneration paradox", + author = "Zhong, Jixing and Aires, Rita and Tsissios, Georgios and Skoufa, + Evangelia and Brandt, Kerstin and Sandoval-Guzm{\'a}n, Tatiana + and Aztekin, Can", + abstract = "Humans and other tetrapods are considered to require + apical-ectodermal-ridge (AER) cells for limb development, and + AER-like cells are suggested to be re-formed to initiate limb + regeneration. Paradoxically, the presence of AER in the axolotl, + a primary model organism for regeneration, remains + controversial. Here, by leveraging a single-cell + transcriptomics-based multi-species atlas, composed of axolotl, + human, mouse, chicken, and frog cells, we first establish that + axolotls contain cells with AER characteristics. Further + analyses and spatial transcriptomics reveal that axolotl limbs + do not fully re-form AER cells during regeneration. Moreover, + the axolotl mesoderm displays part of the AER machinery, + revealing a program for limb (re)growth. These results clarify + the debate about the axolotl AER and the extent to which the + limb developmental program is recapitulated during regeneration.", + journal = "Nat. Commun.", + publisher = "Springer Science and Business Media LLC", + volume = 14, + number = 1, + pages = "6346", + month = oct, + year = 2023, + copyright = "https://creativecommons.org/licenses/by/4.0", + language = "en" +} + +@ARTICLE{Lequain2023-md, + title = "Spatial transcriptomics reveals signatures of histopathological + changes in muscular sarcoidosis", + author = "Lequain, Hippolyte and D{\'e}gletagne, Cyril and Streichenberger, + Nathalie and Valantin, Julie and Simonet, Thomas and Schaeffer, + Laurent and S{\`e}ve, Pascal and Leblanc, Pascal", + abstract = "Sarcoidosis is a multisystemic disease characterized by + non-caseating granuloma infiltrating various organs. The form + with symptomatic muscular involvement is called muscular + sarcoidosis. The impact of immune cells composing the granuloma + on the skeletal muscle is misunderstood. Here, we investigated + the granuloma-skeletal muscle interactions through spatial + transcriptomics on two patients affected by muscular sarcoidosis. + Five major transcriptomic clusters corresponding to + perigranuloma, granuloma, and three successive muscle tissue + areas (proximal, intermediate, and distal) around the granuloma + were identified. Analyses revealed upregulated pathways in the + granuloma corresponding to the activation of T-lymphocytes and + monocytes/macrophages cytokines, the upregulation of + extracellular matrix signatures, and the induction of the + TGF-$\beta$ signaling in the perigranuloma. A comparison between + the proximal and distal muscles to the granuloma revealed an + inverse correlation between the distance to the granuloma and the + upregulation of cellular response to + interferon-$\gamma$/$\alpha$, TNF-$\alpha$, IL-1,4,6, fibroblast + proliferation, epithelial to mesenchymal cell transition, and the + downregulation of muscle gene expression. These data shed light + on the intercommunications between granulomas and the muscle + tissue and provide pathophysiological mechanisms by showing that + granuloma immune cells have a direct impact on proximal muscle + tissue by promoting its progressive replacement by fibrosis via + the expression of pro-inflammatory and profibrosing signatures. + These data could possibly explain the evolution towards a state + of disability for some patients.", + journal = "Cells", + volume = 12, + number = 23, + month = nov, + year = 2023, + keywords = "Visium; fibrosis; granuloma; muscular sarcoidosis; skeletal + muscle; spatial transcriptomic", + language = "en" +} + +@ARTICLE{Yu2024-eh, + title = "Spatial transcriptomics reveals a low extent of + transcriptionally active hepatitis {B} virus integration in + patients with {HBsAg} loss", + author = "Yu, Xiaoqi and Gong, Qiming and Yu, Demin and Chen, Yongyan and + Jing, Ying and Zoulim, Fabien and Zhang, Xinxin", + abstract = "OBJECTIVE: Hepatitis B virus (HBV) can integrate into the + chromosomes of infected hepatocytes, contributing to the + production of hepatitis B surface antigen (HBsAg) and to + hepatocarcinogenesis. In this study, we aimed to explore whether + transcriptionally active HBV integration events spread + throughout the liver tissue in different phases of chronic HBV + infection, especially in patients with HBsAg loss. DESIGN: We + constructed high-resolution spatial transcriptomes of liver + biopsies containing 13 059 tissue spots from 18 patients with + chronic HBV infection to analyse the occurrence and relative + distribution of transcriptionally active viral integration + events. Immunohistochemistry was performed to evaluate the + expression of HBsAg and HBV core antigen. Intrahepatic + covalently closed circular DNA (cccDNA) levels were quantified + by real-time qPCR. RESULTS: Spatial transcriptome sequencing + identified the presence of 13 154 virus-host chimeric reads in + 7.86\% (1026 of 13 059) of liver tissue spots in all patients, + including three patients with HBsAg loss. These HBV integration + sites were randomly distributed on chromosomes and can localise + in host genes involved in hepatocarcinogenesis, such as ALB, CLU + and APOB. Patients who were receiving or had received antiviral + treatment had a significantly lower percentage of viral + integration-containing spots and significantly fewer chimeric + reads than treatment-na{\"\i}ve patients. Intrahepatic cccDNA + levels correlated well with viral integration events. + CONCLUSION: Transcriptionally active HBV integration occurred in + chronically HBV-infected patients at different phases, including + in patients with HBsAg loss. Antiviral treatment was associated + with a decreased number and extent of transcriptionally active + viral integrations, implying that early treatment intervention + may further reduce the number of viral integration events.", + journal = "Gut", + publisher = "BMJ", + volume = 73, + number = 5, + pages = "797--809", + month = apr, + year = 2024, + keywords = "chronic viral hepatitis; hepatitis B; liver biopsy", + language = "en" +} + +@ARTICLE{Ng2024-ut, + title = "Deterministic reprogramming of neutrophils within tumors", + author = "Ng, Melissa S F and Kwok, Immanuel and Tan, Leonard and Shi, + Changming and Cerezo-Wallis, Daniela and Tan, Yingrou and Leong, + Keith and Calvo, Gabriel F and Yang, Katharine and Zhang, Yuning + and Jin, Jingsi and Liong, Ka Hang and Wu, Dandan and He, Rui and + Liu, Dehua and Teh, Ye Chean and Bleriot, Camille and Caronni, + Nicoletta and Liu, Zhaoyuan and Duan, Kaibo and Narang, Vipin and + Ballesteros, Iv{\'a}n and Moalli, Federica and Li, Mengwei and + Chen, Jinmiao and Liu, Yao and Liu, Lianxin and Qi, Jingjing and + Liu, Yingbin and Jiang, Lingxi and Shen, Baiyong and Cheng, Hui + and Cheng, Tao and Angeli, Veronique and Sharma, Ankur and Loh, + Yuin-Han and Tey, Hong Liang and Chong, Shu Zhen and Iannacone, + Matteo and Ostuni, Renato and Hidalgo, Andr{\'e}s and Ginhoux, + Florent and Ng, Lai Guan", + abstract = "Neutrophils are increasingly recognized as key players in the + tumor immune response and are associated with poor clinical + outcomes. Despite recent advances characterizing the diversity of + neutrophil states in cancer, common trajectories and mechanisms + governing the ontogeny and relationship between these neutrophil + states remain undefined. Here, we demonstrate that immature and + mature neutrophils that enter tumors undergo irreversible + epigenetic, transcriptional, and proteomic modifications to + converge into a distinct, terminally differentiated dcTRAIL-R1+ + state. Reprogrammed dcTRAIL-R1+ neutrophils predominantly + localize to a glycolytic and hypoxic niche at the tumor core and + exert pro-angiogenic function that favors tumor growth. We found + similar trajectories in neutrophils across multiple tumor types + and in humans, suggesting that targeting this program may provide + a means of enhancing certain cancer immunotherapies.", + journal = "Science", + volume = 383, + number = 6679, + pages = "eadf6493", + month = jan, + year = 2024, + language = "en" +} + +@ARTICLE{Cherief2023-hx, + title = "{TrkA-mediated} sensory innervation of injured mouse tendon + supports tendon sheath progenitor cell expansion and tendon + repair", + author = "Cherief, Masnsen and Xu, Jiajia and Li, Zhao and Tower, Robert J + and Ramesh, Sowmya and Qin, Qizhi and Gomez-Salazar, Mario and + Yea, Ji-Hye and Lee, Seungyong and Negri, Stefano and Xu, Mingxin + and Price, Theodore and Kendal, Adrian R and Fan, Chen-Ming and + Clemens, Thomas L and Levi, Benjamin and James, Aaron W", + abstract = "Peripheral neurons terminate at the surface of tendons partly to + relay nociceptive pain signals; however, the role of peripheral + nerves in tendon injury and repair remains unclear. Here, we show + that after Achilles tendon injury in mice, there is new nerve + growth near tendon cells that express nerve growth factor (NGF). + Conditional deletion of the Ngf gene in either myeloid or + mesenchymal mouse cells limited both innervation and tendon + repair. Similarly, inhibition of the NGF receptor tropomyosin + receptor kinase A (TrkA) abrogated tendon healing in mouse tendon + injury. Sural nerve transection blocked the postinjury increase + in tendon sensory innervation and the expansion of tendon sheath + progenitor cells (TSPCs) expressing tubulin polymerization + promoting protein family member 3. Single cell and spatial + transcriptomics revealed that disruption of sensory innervation + resulted in dysregulated inflammatory signaling and transforming + growth factor-$\beta$ (TGF$\beta$) signaling in injured mouse + tendon. Culture of mouse TSPCs with conditioned medium from + dorsal root ganglia neuron further supported a role for neuronal + mediators and TGF$\beta$ signaling in TSPC proliferation. + Transcriptomic and histologic analyses of injured human tendon + biopsy samples supported a role for innervation and TGF$\beta$ + signaling in human tendon regeneration. Last, treating mice after + tendon injury systemically with a small-molecule partial agonist + of TrkA increased neurovascular response, TGF$\beta$ signaling, + TSPC expansion, and tendon tissue repair. Although further + studies should investigate the potential effects of denervation + on mechanical loading of tendon, our results suggest that + peripheral innervation is critical for the regenerative response + after acute tendon injury.", + journal = "Sci. Transl. Med.", + volume = 15, + number = 727, + pages = "eade4619", + month = dec, + year = 2023, + language = "en" +} + +@ARTICLE{Rahimikollu2024-fs, + title = "{SLIDE}: Significant Latent Factor Interaction Discovery and + Exploration across biological domains", + author = "Rahimikollu, Javad and Xiao, Hanxi and Rosengart, Annaelaine and + Rosen, Aaron B I and Tabib, Tracy and Zdinak, Paul M and He, Kun + and Bing, Xin and Bunea, Florentina and Wegkamp, Marten and + Poholek, Amanda C and Joglekar, Alok V and Lafyatis, Robert A and + Das, Jishnu", + abstract = "Modern multiomic technologies can generate deep multiscale + profiles. However, differences in data modalities, + multicollinearity of the data, and large numbers of irrelevant + features make analyses and integration of high-dimensional omic + datasets challenging. Here we present Significant Latent Factor + Interaction Discovery and Exploration (SLIDE), a first-in-class + interpretable machine learning technique for identifying + significant interacting latent factors underlying outcomes of + interest from high-dimensional omic datasets. SLIDE makes no + assumptions regarding data-generating mechanisms, comes with + theoretical guarantees regarding identifiability of the latent + factors/corresponding inference, and has rigorous false discovery + rate control. Using SLIDE on single-cell and spatial omic + datasets, we uncovered significant interacting latent factors + underlying a range of molecular, cellular and organismal + phenotypes. SLIDE outperforms/performs at least as well as a wide + range of state-of-the-art approaches, including other latent + factor approaches. More importantly, it provides biological + inference beyond prediction that other methods do not afford. + Thus, SLIDE is a versatile engine for biological discovery from + modern multiomic datasets.", + journal = "Nat. Methods", + month = feb, + year = 2024, + language = "en" +} + +@ARTICLE{Lowe2024-nf, + title = "Tertiary lymphoid structures sustain cutaneous {B} cell activity + in hidradenitis suppurativa", + author = "Lowe, Margaret M and Cohen, Jarish N and Moss, Madison I and + Clancy, Sean and Adler, James P and Yates, Ashley E and Naik, + Haley B and Yadav, Rashi and Pauli, Mariela and Taylor, Ian and + McKay, Austin and Harris, Hobart and Kim, Esther and Hansen, + Scott L and Rosenblum, Michael D and Moreau, Joshua M", + abstract = "Hidradenitis suppurativa (HS) is a chronic skin condition + affecting approximately 1\% of the US population. HS skin lesions + are highly inflammatory and characterized by a large immune + infiltrate. While B cells and plasma cells comprise a major + component of this immune milieu, the biology and the contribution + of these cells in HS pathogenesis are unclear. We aimed to + investigate the dynamics and microenvironmental interactions of B + cells within cutaneous HS lesions. Combining histological + analysis, single-cell RNA sequencing, and spatial transcriptomics + profiling of HS lesions, we defined the tissue microenvironment + relative to B cell activity within this disease. Our findings + identified tertiary lymphoid structures (TLSs) within HS lesions + and described organized interactions among T cells, B cells, + antigen-presenting cells, and skin stroma. We found evidence that + B cells within HS TLSs actively underwent maturation, including + participation in germinal center reactions and class switch + recombination. Moreover, skin stroma and accumulating T cells + were primed to support the formation of TLSs and facilitate B + cell recruitment during HS. Our data definitively demonstrated + the presence of TLSs in lesional HS skin and point to ongoing + cutaneous B cell maturation through class switch recombination + and affinity maturation during disease progression in this + inflamed nonlymphoid tissue.", + journal = "JCI Insight", + volume = 9, + number = 3, + month = feb, + year = 2024, + keywords = "Adaptive immunity; Dermatology; Immunology; Skin", + language = "en" +} + +% The entry below contains non-ASCII chars that could not be converted +% to a LaTeX equivalent. +@ARTICLE{Cortese2023-sc, + title = "High-resolution analysis of mononuclear phagocytes reveals + {GPNMB} as a prognostic marker in human colorectal liver + metastasis", + author = "Cortese, Nina and Carriero, Roberta and Barbagallo, Marialuisa + and Putignano, Anna Rita and Costa, Guido and Giavazzi, Fabio + and Grizzi, Fabio and Pasqualini, Fabio and Peano, Clelia and + Basso, Gianluca and Marchini, Sergio and Colombo, Federico + Simone and Soldani, Cristiana and Franceschini, Barbara and Di + Tommaso, Luca and Terracciano, Luigi and Donadon, Matteo and + Torzilli, Guido and Kunderfranco, Paolo and Mantovani, Alberto + and Marchesi, Federica", + abstract = "Patients with colorectal liver metastasis (CLM) present with + heterogenous clinical outcomes and improved classification is + needed to ameliorate the therapeutic output. Macrophages (Mϕ) + hold promise as prognostic classifiers and therapeutic targets. + Here, stemming from a single-cell analysis of mononuclear + phagocytes infiltrating human CLM, we identified two Mϕ markers + associated with distinct populations with opposite clinical + relevance. The invasive margin of CLM was enriched in + pro-inflammatory monocyte-derived Mϕ (MoMϕ) expressing the + monocytic marker SERPINB2, and a more differentiated population, + tumor-associated Mϕ (TAM), expressing glycoprotein nonmetastatic + melanoma protein B (GPNMB). SERPINB2+ MoMϕ had an early + inflammatory profile, whereas GPNMB+ TAMs were enriched in + pathways of matrix degradation, angiogenesis, and lipid + metabolism and were found closer to the tumor margin, as + confirmed by spatial transcriptomics on CLM specimens. In a + cohort of patients, a high infiltration of SERPINB2+ cells + independently associated with longer disease-free survival (DFS; + P = 0.033), whereas a high density of GPNMB+ cells correlated + with shorter DFS (P = 0.012) and overall survival (P = 0.002). + Cell-cell interaction analysis defined opposing roles for MoMϕ + and TAMs, suggesting that SERPINB2+ and GPNMB+ cells are + discrete populations of Mϕ and may be exploited for further + translation to an immune-based stratification tool. This study + provides evidence of how multi-omics approaches can identify + nonredundant, clinically relevant markers for further + translation to immune-based patient stratification tools and + therapeutic targets. GPNMB has been shown to set Mϕ in an + immunosuppressive mode. Our high dimensional analyses provide + further evidence that GPNMB is a negative prognostic indicator + and a potential player in the protumor function of Mϕ + populations.", + journal = "Cancer Immunol. Res.", + publisher = "American Association for Cancer Research (AACR)", + volume = 11, + number = 4, + pages = "405--420", + month = apr, + year = 2023, + language = "en" +} + +@ARTICLE{Huuki-Myers2023-ix, + title = "Integrated single cell and unsupervised spatial transcriptomic + analysis defines molecular anatomy of the human dorsolateral + prefrontal cortex", + author = "Huuki-Myers, Louise and Spangler, Abby and Eagles, Nick and + Montgomery, Kelsey D and Kwon, Sang Ho and Guo, Boyi and + Grant-Peters, Melissa and Divecha, Heena R and Tippani, Madhavi + and Sriworarat, Chaichontat and Nguyen, Annie B and Ravichandran, + Prashanthi and Tran, Matthew N and Seyedian, Arta and + {PsychENCODE consortium} and Hyde, Thomas M and Kleinman, Joel E + and Battle, Alexis and Page, Stephanie C and Ryten, Mina and + Hicks, Stephanie C and Martinowich, Keri and Collado-Torres, + Leonardo and Maynard, Kristen R", + abstract = "Generation of a molecular neuroanatomical map of the human + prefrontal cortex reveals novel spatial domains and cell-cell + interactions relevant for psychiatric disease. The molecular + organization of the human neocortex has been historically studied + in the context of its histological layers. However, emerging + spatial transcriptomic technologies have enabled unbiased + identification of transcriptionally-defined spatial domains that + move beyond classic cytoarchitecture. Here we used the Visium + spatial gene expression platform to generate a data-driven + molecular neuroanatomical atlas across the anterior-posterior + axis of the human dorsolateral prefrontal cortex (DLPFC). + Integration with paired single nucleus RNA-sequencing data + revealed distinct cell type compositions and cell-cell + interactions across spatial domains. Using PsychENCODE and + publicly available data, we map the enrichment of cell types and + genes associated with neuropsychiatric disorders to discrete + spatial domains. Finally, we provide resources for the scientific + community to explore these integrated spatial and single cell + datasets at research.libd.org/spatialDLPFC/.", + journal = "bioRxivorg", + month = feb, + year = 2023, + language = "en" +} + +@ARTICLE{Maynard2021-wa, + title = "Transcriptome-scale spatial gene expression in the human + dorsolateral prefrontal cortex", + author = "Maynard, Kristen R and Collado-Torres, Leonardo and Weber, Lukas + M and Uytingco, Cedric and Barry, Brianna K and Williams, + Stephen R and Catallini, 2nd, Joseph L and Tran, Matthew N and + Besich, Zachary and Tippani, Madhavi and Chew, Jennifer and Yin, + Yifeng and Kleinman, Joel E and Hyde, Thomas M and Rao, Nikhil + and Hicks, Stephanie C and Martinowich, Keri and Jaffe, Andrew E", + abstract = "We used the 10x Genomics Visium platform to define the spatial + topography of gene expression in the six-layered human + dorsolateral prefrontal cortex. We identified extensive + layer-enriched expression signatures and refined associations to + previous laminar markers. We overlaid our laminar expression + signatures on large-scale single nucleus RNA-sequencing data, + enhancing spatial annotation of expression-driven clusters. By + integrating neuropsychiatric disorder gene sets, we showed + differential layer-enriched expression of genes associated with + schizophrenia and autism spectrum disorder, highlighting the + clinical relevance of spatially defined expression. We then + developed a data-driven framework to define unsupervised + clusters in spatial transcriptomics data, which can be applied + to other tissues or brain regions in which morphological + architecture is not as well defined as cortical laminae. Last, + we created a web application for the scientific community to + explore these raw and summarized data to augment ongoing + neuroscience and spatial transcriptomics research ( + http://research.libd.org/spatialLIBD ).", + journal = "Nat. Neurosci.", + publisher = "Springer Science and Business Media LLC", + volume = 24, + number = 3, + pages = "425--436", + month = mar, + year = 2021, + language = "en" +} + +@ARTICLE{Wu2021-zq, + title = "A single-cell and spatially resolved atlas of human breast + cancers", + author = "Wu, Sunny Z and Al-Eryani, Ghamdan and Roden, Daniel Lee and + Junankar, Simon and Harvey, Kate and Andersson, Alma and + Thennavan, Aatish and Wang, Chenfei and Torpy, James R and + Bartonicek, Nenad and Wang, Taopeng and Larsson, Ludvig and + Kaczorowski, Dominik and Weisenfeld, Neil I and Uytingco, Cedric + R and Chew, Jennifer G and Bent, Zachary W and Chan, Chia-Ling + and Gnanasambandapillai, Vikkitharan and Dutertre, + Charles-Antoine and Gluch, Laurence and Hui, Mun N and Beith, + Jane and Parker, Andrew and Robbins, Elizabeth and Segara, + Davendra and Cooper, Caroline and Mak, Cindy and Chan, Belinda + and Warrier, Sanjay and Ginhoux, Florent and Millar, Ewan and + Powell, Joseph E and Williams, Stephen R and Liu, X Shirley and + O'Toole, Sandra and Lim, Elgene and Lundeberg, Joakim and Perou, + Charles M and Swarbrick, Alexander", + abstract = "Breast cancers are complex cellular ecosystems where heterotypic + interactions play central roles in disease progression and + response to therapy. However, our knowledge of their cellular + composition and organization is limited. Here we present a + single-cell and spatially resolved transcriptomics analysis of + human breast cancers. We developed a single-cell method of + intrinsic subtype classification (SCSubtype) to reveal recurrent + neoplastic cell heterogeneity. Immunophenotyping using cellular + indexing of transcriptomes and epitopes by sequencing (CITE-seq) + provides high-resolution immune profiles, including new + PD-L1/PD-L2+ macrophage populations associated with clinical + outcome. Mesenchymal cells displayed diverse functions and + cell-surface protein expression through differentiation within + three major lineages. Stromal-immune niches were spatially + organized in tumors, offering insights into antitumor immune + regulation. Using single-cell signatures, we deconvoluted large + breast cancer cohorts to stratify them into nine clusters, + termed 'ecotypes', with unique cellular compositions and + clinical outcomes. This study provides a comprehensive + transcriptional atlas of the cellular architecture of breast + cancer.", + journal = "Nat. Genet.", + publisher = "Springer Science and Business Media LLC", + volume = 53, + number = 9, + pages = "1334--1347", + month = sep, + year = 2021, + language = "en" +} + +@ARTICLE{Kuppe2022-zy, + title = "Spatial multi-omic map of human myocardial infarction", + author = "Kuppe, Christoph and Ramirez Flores, Ricardo O and Li, Zhijian + and Hayat, Sikander and Levinson, Rebecca T and Liao, Xian and + Hannani, Monica T and Tanevski, Jovan and W{\"u}nnemann, Florian + and Nagai, James S and Halder, Maurice and Schumacher, David and + Menzel, Sylvia and Sch{\"a}fer, Gideon and Hoeft, Konrad and + Cheng, Mingbo and Ziegler, Susanne and Zhang, Xiaoting and + Peisker, Fabian and Kaesler, Nadine and Saritas, Turgay and Xu, + Yaoxian and Kassner, Astrid and Gummert, Jan and Morshuis, + Michiel and Amrute, Junedh and Veltrop, Rogier J A and Boor, + Peter and Klingel, Karin and Van Laake, Linda W and Vink, Aryan + and Hoogenboezem, Remco M and Bindels, Eric M J and Schurgers, + Leon and Sattler, Susanne and Schapiro, Denis and Schneider, + Rebekka K and Lavine, Kory and Milting, Hendrik and Costa, Ivan + G and Saez-Rodriguez, Julio and Kramann, Rafael", + abstract = "Myocardial infarction is a leading cause of death worldwide1. + Although advances have been made in acute treatment, an + incomplete understanding of remodelling processes has limited + the effectiveness of therapies to reduce late-stage mortality2. + Here we generate an integrative high-resolution map of human + cardiac remodelling after myocardial infarction using + single-cell gene expression, chromatin accessibility and spatial + transcriptomic profiling of multiple physiological zones at + distinct time points in myocardium from patients with myocardial + infarction and controls. Multi-modal data integration enabled us + to evaluate cardiac cell-type compositions at increased + resolution, yielding insights into changes of the cardiac + transcriptome and epigenome through the identification of + distinct tissue structures of injury, repair and remodelling. We + identified and validated disease-specific cardiac cell states of + major cell types and analysed them in their spatial context, + evaluating their dependency on other cell types. Our data + elucidate the molecular principles of human myocardial tissue + organization, recapitulating a gradual cardiomyocyte and myeloid + continuum following ischaemic injury. In sum, our study provides + an integrative molecular map of human myocardial infarction, + represents an essential reference for the field and paves the + way for advanced mechanistic and therapeutic studies of cardiac + disease.", + journal = "Nature", + publisher = "Springer Science and Business Media LLC", + volume = 608, + number = 7924, + pages = "766--777", + month = aug, + year = 2022, + language = "en" +} + +@ARTICLE{Erickson2022-ia, + title = "Spatially resolved clonal copy number alterations in benign and + malignant tissue", + author = "Erickson, Andrew and He, Mengxiao and Berglund, Emelie and + Marklund, Maja and Mirzazadeh, Reza and Schultz, Niklas and + Kvastad, Linda and Andersson, Alma and Bergenstr{\aa}hle, Ludvig + and Bergenstr{\aa}hle, Joseph and Larsson, Ludvig and Alonso + Galicia, Leire and Shamikh, Alia and Basmaci, Elisa and + D{\'\i}az De St{\aa}hl, Teresita and Rajakumar, Timothy and + Doultsinos, Dimitrios and Thrane, Kim and Ji, Andrew L and + Khavari, Paul A and Tarish, Firaz and Tanoglidi, Anna and + Maaskola, Jonas and Colling, Richard and Mirtti, Tuomas and + Hamdy, Freddie C and Woodcock, Dan J and Helleday, Thomas and + Mills, Ian G and Lamb, Alastair D and Lundeberg, Joakim", + abstract = "Defining the transition from benign to malignant tissue is + fundamental to improving early diagnosis of cancer1. Here we use + a systematic approach to study spatial genome integrity in situ + and describe previously unidentified clonal relationships. We + used spatially resolved transcriptomics2 to infer spatial copy + number variations in >120,000 regions across multiple organs, in + benign and malignant tissues. We demonstrate that genome-wide + copy number variation reveals distinct clonal patterns within + tumours and in nearby benign tissue using an organ-wide approach + focused on the prostate. Our results suggest a model for how + genomic instability arises in histologically benign tissue that + may represent early events in cancer evolution. We highlight the + power of capturing the molecular and spatial continuums in a + tissue context and challenge the rationale for treatment + paradigms, including focal therapy.", + journal = "Nature", + publisher = "Springer Science and Business Media LLC", + volume = 608, + number = 7922, + pages = "360--367", + month = aug, + year = 2022, + copyright = "https://creativecommons.org/licenses/by/4.0", + language = "en" +}