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Article ; Online: Remodeling of colon plasma cell repertoire within ulcerative colitis patients.

Scheid, Johannes F / Eraslan, Basak / Hudak, Andrew / Brown, Eric M / Sergio, Dallis / Delorey, Toni M / Phillips, Devan / Lefkovith, Ariel / Jess, Alison T / Duck, Lennard W / Elson, Charles O / Vlamakis, Hera / Plichta, Damian R / Deguine, Jacques / Ananthakrishnan, Ashwin N / Graham, Daniel B / Regev, Aviv / Xavier, Ramnik J

The Journal of experimental medicine

2023 Volume 220, Issue 4

Abstract: Plasma cells (PCs) constitute a significant fraction of colonic mucosal cells and contribute to inflammatory infiltrates in ulcerative colitis (UC). While gut PCs secrete bacteria-targeting IgA antibodies, their role in UC pathogenesis is unknown. We ... ...

Abstract	Plasma cells (PCs) constitute a significant fraction of colonic mucosal cells and contribute to inflammatory infiltrates in ulcerative colitis (UC). While gut PCs secrete bacteria-targeting IgA antibodies, their role in UC pathogenesis is unknown. We performed single-cell V(D)J- and RNA-seq on sorted B cells from the colon of healthy individuals and patients with UC. A large fraction of B cell clones is shared between different colon regions, but inflammation in UC broadly disrupts this landscape, causing transcriptomic changes characterized by an increase in the unfolded protein response (UPR) and antigen presentation genes, clonal expansion, and isotype skewing from IgA1 and IgA2 to IgG1. We also directly expressed and assessed the specificity of 152 mAbs from expanded PC clones. These mAbs show low polyreactivity and autoreactivity and instead target both shared bacterial antigens and specific bacterial strains. Altogether, our results characterize the microbiome-specific colon PC response and how its disruption might contribute to inflammation in UC.
MeSH term(s)	Humans ; Colitis, Ulcerative/genetics ; Plasma Cells ; Colon ; Inflammation/metabolism ; Antigens, Bacterial ; Bacteria ; Immunoglobulin A/metabolism ; Intestinal Mucosa
Chemical Substances	Antigens, Bacterial ; Immunoglobulin A
Language	English
Publishing date	2023-02-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20220538
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Article: Systematically characterizing the roles of E3-ligase family members in inflammatory responses with massively parallel Perturb-seq.

bioRxiv : the preprint server for biology

2023

Abstract: E3 ligases regulate key processes, but many of their roles remain unknown. Using Perturb-seq, we interrogated the function of 1,130 E3 ligases, partners and substrates in the inflammatory response in primary dendritic cells (DCs). Dozens impacted the ... ...

Abstract	E3 ligases regulate key processes, but many of their roles remain unknown. Using Perturb-seq, we interrogated the function of 1,130 E3 ligases, partners and substrates in the inflammatory response in primary dendritic cells (DCs). Dozens impacted the balance of DC1, DC2, migratory DC and macrophage states and a gradient of DC maturation. Family members grouped into co-functional modules that were enriched for physical interactions and impacted specific programs through substrate transcription factors. E3s and their adaptors co-regulated the same processes, but partnered with different substrate recognition adaptors to impact distinct aspects of the DC life cycle. Genetic interactions were more prevalent within than between modules, and a deep learning model, comβVAE, predicts the outcome of new combinations by leveraging modularity. The E3 regulatory network was associated with heritable variation and aberrant gene expression in immune cells in human inflammatory diseases. Our study provides a general approach to dissect gene function.
Language	English
Publishing date	2023-01-24
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.01.23.525198
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Article ; Online: Joint single-cell measurements of nuclear proteins and RNA in vivo.

Chung, Hattie / Parkhurst, Christopher N / Magee, Emma M / Phillips, Devan / Habibi, Ehsan / Chen, Fei / Yeung, Bertrand Z / Waldman, Julia / Artis, David / Regev, Aviv

Nature methods

2021 Volume 18, Issue 10, Page(s) 1204–1212

Abstract: Identifying gene-regulatory targets of nuclear proteins in tissues is a challenge. Here we describe intranuclear cellular indexing of transcriptomes and epitopes (inCITE-seq), a scalable method that measures multiplexed intranuclear protein levels and ... ...

Abstract	Identifying gene-regulatory targets of nuclear proteins in tissues is a challenge. Here we describe intranuclear cellular indexing of transcriptomes and epitopes (inCITE-seq), a scalable method that measures multiplexed intranuclear protein levels and the transcriptome in parallel across thousands of nuclei, enabling joint analysis of transcription factor (TF) levels and gene expression in vivo. We apply inCITE-seq to characterize cell state-related changes upon pharmacological induction of neuronal activity in the mouse brain. Modeling gene expression as a linear combination of quantitative protein levels revealed genome-wide associations of each TF and recovered known gene targets. TF-associated genes were coexpressed as distinct modules that each reflected positive or negative TF levels, showing that our approach can disentangle relative putative contributions of TFs to gene expression and add interpretability to inferred gene networks. inCITE-seq can illuminate how combinations of nuclear proteins shape gene expression in native tissue contexts, with direct applications to solid or frozen tissues and clinical specimens.
MeSH term(s)	Animals ; Antibodies ; Brain/metabolism ; Computational Biology/methods ; Gene Expression Regulation/physiology ; Genome-Wide Association Study ; Kainic Acid/toxicity ; Mice ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; RNA ; Reproducibility of Results ; Seizures/chemically induced ; Single-Cell Analysis/methods ; Transcription Factor RelA/genetics ; Transcription Factor RelA/metabolism
Chemical Substances	Antibodies ; Nuclear Proteins ; Transcription Factor RelA ; RNA (63231-63-0) ; Kainic Acid (SIV03811UC)
Language	English
Publishing date	2021-10-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2169522-2
ISSN	1548-7105 ; 1548-7091
ISSN (online)	1548-7105
ISSN	1548-7091
DOI	10.1038/s41592-021-01278-1
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Article ; Online: Cell subtype-specific effects of genetic variation in the Alzheimer's disease brain.

Fujita, Masashi / Gao, Zongmei / Zeng, Lu / McCabe, Cristin / White, Charles C / Ng, Bernard / Green, Gilad Sahar / Rozenblatt-Rosen, Orit / Phillips, Devan / Amir-Zilberstein, Liat / Lee, Hyo / Pearse, Richard V / Khan, Atlas / Vardarajan, Badri N / Kiryluk, Krzysztof / Ye, Chun Jimmie / Klein, Hans-Ulrich / Wang, Gao / Regev, Aviv /

Habib, Naomi / Schneider, Julie A / Wang, Yanling / Young-Pearse, Tracy / Mostafavi, Sara / Bennett, David A / Menon, Vilas / De Jager, Philip L

Nature genetics

2024 Volume 56, Issue 4, Page(s) 605–614

Abstract: The relationship between genetic variation and gene expression in brain cell types and subtypes remains understudied. Here, we generated single-nucleus RNA sequencing data from the neocortex of 424 individuals of advanced age; we assessed the effect of ... ...

Abstract	The relationship between genetic variation and gene expression in brain cell types and subtypes remains understudied. Here, we generated single-nucleus RNA sequencing data from the neocortex of 424 individuals of advanced age; we assessed the effect of genetic variants on RNA expression in cis (cis-expression quantitative trait loci) for seven cell types and 64 cell subtypes using 1.5 million transcriptomes. This effort identified 10,004 eGenes at the cell type level and 8,099 eGenes at the cell subtype level. Many eGenes are only detected within cell subtypes. A new variant influences APOE expression only in microglia and is associated with greater cerebral amyloid angiopathy but not Alzheimer's disease pathology, after adjusting for APOEε4, providing mechanistic insights into both pathologies. Furthermore, only a TMEM106B variant affects the proportion of cell subtypes. Integration of these results with genome-wide association studies highlighted the targeted cell type and probable causal gene within Alzheimer's disease, schizophrenia, educational attainment and Parkinson's disease loci.
MeSH term(s)	Humans ; Alzheimer Disease/metabolism ; Genome-Wide Association Study/methods ; Brain/metabolism ; Quantitative Trait Loci/genetics ; Genetic Variation/genetics ; Membrane Proteins/genetics ; Nerve Tissue Proteins/genetics
Chemical Substances	TMEM106B protein, human ; Membrane Proteins ; Nerve Tissue Proteins
Language	English
Publishing date	2024-03-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-024-01685-y
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Zs.A 3613: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Functional analyses and single cell immunoprofiling uncover sex-specific differences in SARS-CoV2 immune memory development.

Eraslan, Basak / Brown, Eric / Benson, Maura / Amir-Zilberstein, Liat / Park, Sung-Moo / Tusi, Betsabeh / Pokatayev, Vladislav / Hecht, Cody / Pishesha, Novalia / Phillips, Devan / Kim, Andy / Zhang, Shuting / Gaca, Anthony / Ghantous, Fadi / Delorey, Toni / Livny, Jonathan / Baden, Lindsey / Rozenblatt-Rosen, Orit / Graham, Daniel /

Regev, Aviv / Seaman, Michael / Woolley, Ann / Cosimi, Lisa / Hung, Deborah / Deguine, Jacques / Xavier, Ramnik

Research square

2022

Abstract: SARS-CoV-2 infection leads to a broad range of outcomes and immune responses, with the development of neutralizing antibodies generally correlated with protection against reinfection. Here, we have characterized both neutralizing activity and T cell ... ...

Abstract	SARS-CoV-2 infection leads to a broad range of outcomes and immune responses, with the development of neutralizing antibodies generally correlated with protection against reinfection. Here, we have characterized both neutralizing activity and T cell responses in a cluster of subjects with mild disease linked to a single spreading event. Surprisingly, we observed sex-specific associations between spike- and particularly nucleoprotein-specific T cell responses and neutralization, with pro-inflammatory cytokines being linked to higher titers only in males. Using single cell immunoprofiling, which provided matched transcriptome and T-cell receptor (TCR) profiles in restimulated CD4 + and CD8 + cells from these subjects, we identified differences in type I IFN signaling that may underlie this difference in antibody generation. Finally, we also identified several TCRs associated with cytokine producing T cells. Altogether, our work maps the breadth of immunological outcomes of SARS-CoV2 infections and highlight the potential role of sex-specific feedback loops during the generation of neutralizing antibodies.
Language	English
Publishing date	2022-03-15
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-1416969/v1
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Article ; Online: Stepwise-edited, human melanoma models reveal mutations' effect on tumor and microenvironment.

Science (New York, N.Y.)

2022 Volume 376, Issue 6592, Page(s) eabi8175

Abstract: Establishing causal relationships between genetic alterations of human cancers and specific phenotypes of malignancy remains a challenge. We sequentially introduced mutations into healthy human melanocytes in up to five genes spanning six commonly ... ...

Abstract	Establishing causal relationships between genetic alterations of human cancers and specific phenotypes of malignancy remains a challenge. We sequentially introduced mutations into healthy human melanocytes in up to five genes spanning six commonly disrupted melanoma pathways, forming nine genetically distinct cellular models of melanoma. We connected mutant melanocyte genotypes to malignant cell expression programs in vitro and in vivo, replicative immortality, malignancy, rapid tumor growth, pigmentation, metastasis, and histopathology. Mutations in malignant cells also affected tumor microenvironment composition and cell states. Our melanoma models shared genotype-associated expression programs with patient melanomas, and a deep learning model showed that these models partially recapitulated genotype-associated histopathological features as well. Thus, a progressive series of genome-edited human cancer models can causally connect genotypes carrying multiple mutations to phenotype.
MeSH term(s)	Humans ; Melanocytes/metabolism ; Melanoma/pathology ; Mutation ; Skin Neoplasms/genetics ; Skin Neoplasms/pathology ; Tumor Microenvironment/genetics
Language	English
Publishing date	2022-04-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.abi8175
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Zs.A 27: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The CD155/TIGIT axis promotes and maintains immune evasion in neoantigen-expressing pancreatic cancer.

Freed-Pastor, William A / Lambert, Laurens J / Ely, Zackery A / Pattada, Nimisha B / Bhutkar, Arjun / Eng, George / Mercer, Kim L / Garcia, Ana P / Lin, Lin / Rideout, William M / Hwang, William L / Schenkel, Jason M / Jaeger, Alex M / Bronson, Roderick T / Westcott, Peter M K / Hether, Tyler D / Divakar, Prajan / Reeves, Jason W / Deshpande, Vikram /

Delorey, Toni / Phillips, Devan / Yilmaz, Omer H / Regev, Aviv / Jacks, Tyler

Cancer cell

2021 Volume 39, Issue 10, Page(s) 1342–1360.e14

Abstract: The CD155/TIGIT axis can be co-opted during immune evasion in chronic viral infections and cancer. Pancreatic adenocarcinoma (PDAC) is a highly lethal malignancy, and immune-based strategies to combat this disease have been largely unsuccessful to date. ... ...

Abstract	The CD155/TIGIT axis can be co-opted during immune evasion in chronic viral infections and cancer. Pancreatic adenocarcinoma (PDAC) is a highly lethal malignancy, and immune-based strategies to combat this disease have been largely unsuccessful to date. We corroborate prior reports that a substantial portion of PDAC harbors predicted high-affinity MHC class I-restricted neoepitopes and extend these findings to advanced/metastatic disease. Using multiple preclinical models of neoantigen-expressing PDAC, we demonstrate that intratumoral neoantigen-specific CD8
MeSH term(s)	Animals ; Humans ; Immune Evasion/immunology ; Immunotherapy/methods ; Lymphocytes, Tumor-Infiltrating/metabolism ; Mice ; Pancreatic Neoplasms/immunology ; Receptors, Virus/immunology ; Pancreatic Neoplasms
Chemical Substances	Receptors, Virus ; poliovirus receptor
Language	English
Publishing date	2021-08-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccell.2021.07.007
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Zs.A 5650: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV

Scheid, Johannes F / Barnes, Christopher O / Eraslan, Basak / Hudak, Andrew / Keeffe, Jennifer R / Cosimi, Lisa A / Brown, Eric M / Muecksch, Frauke / Weisblum, Yiska / Zhang, Shuting / Delorey, Toni / Woolley, Ann E / Ghantous, Fadi / Park, Sung-Moo / Phillips, Devan / Tusi, Betsabeh / Huey-Tubman, Kathryn E / Cohen, Alexander A / Gnanapragasam, Priyanthi N.P /

Rzasa, Kara / Hatziioanno, Theodora / Durney, Michael A / Gu, Xiebin / Tada, Takuya / Landau, Nathaniel R / West, Anthony P / Rozenblatt-Rosen, Orit / Seaman, Michael S / Baden, Lindsey R / Graham, Daniel B / Deguine, Jacques / Bieniasz, Paul D / Regev, Aviv / Hung, Deborah / Bjorkman, Pamela J / Xavier, Ramnik J

Cell. 2021 June 10, v. 184, no. 12

2021

Abstract: Monoclonal antibodies (mAbs) are a focus in vaccine and therapeutic design to counteract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. Here, we combined B cell sorting with single-cell VDJ and RNA sequencing (RNA-seq) and ...

Abstract	Monoclonal antibodies (mAbs) are a focus in vaccine and therapeutic design to counteract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. Here, we combined B cell sorting with single-cell VDJ and RNA sequencing (RNA-seq) and mAb structures to characterize B cell responses against SARS-CoV-2. We show that the SARS-CoV-2-specific B cell repertoire consists of transcriptionally distinct B cell populations with cells producing potently neutralizing antibodies (nAbs) localized in two clusters that resemble memory and activated B cells. Cryo-electron microscopy structures of selected nAbs from these two clusters complexed with SARS-CoV-2 spike trimers show recognition of various receptor-binding domain (RBD) epitopes. One of these mAbs, BG10-19, locks the spike trimer in a closed conformation to potently neutralize SARS-CoV-2, the recently arising mutants B.1.1.7 and B.1.351, and SARS-CoV and cross-reacts with heterologous RBDs. Together, our results characterize transcriptional differences among SARS-CoV-2-specific B cells and uncover cross-neutralizing Ab targets that will inform immunogen and therapeutic design against coronaviruses.
Keywords	B-lymphocytes ; RNA ; Severe acute respiratory syndrome coronavirus 2 ; cryo-electron microscopy ; epitopes ; genomics ; memory ; sequence analysis ; therapeutics ; transcription (genetics) ; vaccines
Language	English
Dates of publication	2021-0610
Size	p. 3205-3221.e24.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2021.04.032
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Emergence of a High-Plasticity Cell State during Lung Cancer Evolution.

Marjanovic, Nemanja Despot / Hofree, Matan / Chan, Jason E / Canner, David / Wu, Katherine / Trakala, Marianna / Hartmann, Griffin G / Smith, Olivia C / Kim, Jonathan Y / Evans, Kelly Victoria / Hudson, Anna / Ashenberg, Orr / Porter, Caroline B M / Bejnood, Alborz / Subramanian, Ayshwarya / Pitter, Kenneth / Yan, Yan / Delorey, Toni / Phillips, Devan R /

Shah, Nisargbhai / Chaudhary, Ojasvi / Tsankov, Alexander / Hollmann, Travis / Rekhtman, Natasha / Massion, Pierre P / Poirier, John T / Mazutis, Linas / Li, Ruifang / Lee, Joo-Hyeon / Amon, Angelika / Rudin, Charles M / Jacks, Tyler / Regev, Aviv / Tammela, Tuomas

Cancer cell

2020 Volume 38, Issue 2, Page(s) 229–246.e13

Abstract: Tumor evolution from a single cell into a malignant, heterogeneous tissue remains poorly understood. Here, we profile single-cell transcriptomes of genetically engineered mouse lung tumors at seven stages, from pre-neoplastic hyperplasia to ... ...

Abstract	Tumor evolution from a single cell into a malignant, heterogeneous tissue remains poorly understood. Here, we profile single-cell transcriptomes of genetically engineered mouse lung tumors at seven stages, from pre-neoplastic hyperplasia to adenocarcinoma. The diversity of transcriptional states increases over time and is reproducible across tumors and mice. Cancer cells progressively adopt alternate lineage identities, computationally predicted to be mediated through a common transitional, high-plasticity cell state (HPCS). Accordingly, HPCS cells prospectively isolated from mouse tumors and human patient-derived xenografts display high capacity for differentiation and proliferation. The HPCS program is associated with poor survival across human cancers and demonstrates chemoresistance in mice. Our study reveals a central principle underpinning intra-tumoral heterogeneity and motivates therapeutic targeting of the HPCS.
MeSH term(s)	Animals ; Cell Differentiation/genetics ; Cell Line, Tumor ; Cell Plasticity/genetics ; Cell Proliferation/genetics ; Cells, Cultured ; Disease Models, Animal ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Genetic Heterogeneity ; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Mice ; Neoplastic Stem Cells/metabolism ; Single-Cell Analysis/methods ; Transcriptome/genetics
Language	English
Publishing date	2020-07-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccell.2020.06.012
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Article: A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients.

Pita-Juarez, Yered / Karagkouni, Dimitra / Kalavros, Nikolaos / Melms, Johannes C / Niezen, Sebastian / Delorey, Toni M / Essene, Adam L / Brook, Olga R / Pant, Deepti / Skelton-Badlani, Disha / Naderi, Pourya / Huang, Pinzhu / Pan, Liuliu / Hether, Tyler / Andrews, Tallulah S / Ziegler, Carly G K / Reeves, Jason / Myloserdnyy, Andriy / Chen, Rachel /

Nam, Andy / Phelan, Stefan / Liang, Yan / Amin, Amit Dipak / Biermann, Jana / Hibshoosh, Hanina / Veregge, Molly / Kramer, Zachary / Jacobs, Christopher / Yalcin, Yusuf / Phillips, Devan / Slyper, Michal / Subramanian, Ayshwarya / Ashenberg, Orr / Bloom-Ackermann, Zohar / Tran, Victoria M / Gomez, James / Sturm, Alexander / Zhang, Shuting / Fleming, Stephen J / Warren, Sarah / Beechem, Joseph / Hung, Deborah / Babadi, Mehrtash / Padera, Robert F / MacParland, Sonya A / Bader, Gary D / Imad, Nasser / Solomon, Isaac H / Miller, Eric / Riedel, Stefan / Porter, Caroline B M / Villani, Alexandra-Chloé / Tsai, Linus T-Y / Hide, Winston / Szabo, Gyongyi / Hecht, Jonathan / Rozenblatt-Rosen, Orit / Shalek, Alex K / Izar, Benjamin / Regev, Aviv / Popov, Yury / Jiang, Z Gordon / Vlachos, Ioannis S

bioRxiv : the preprint server for biology

2022

Abstract: The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial ... ...

Abstract	The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. We identified hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells. Integrated analysis and comparisons with healthy controls revealed extensive changes in the cellular composition and expression states in COVID-19 liver, reflecting hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis. We also observed Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas, resembling similar responses in liver injury in mice and in sepsis, respectively. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition was dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells. Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.
Language	English
Publishing date	2022-10-28
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.10.27.514070
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