ArticleGenome biology2025
A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients.
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Article in Genome biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14citing papers in PubMed
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Who cites it
14 citing papers in PubMed.
- Durable response to CAR T is associated with elevated activation and clonotypic expansion of the cytotoxic native T cell repertoire.Nature communications · 2025Trial
- Trimodal, uncertainty-guided whole-slide framework for genome-scale spatial expression and image-only virtual perturbation in cancer cohorts.Genome medicine · 2026Article
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- Spatial architecture of development and disease.Nature reviews. Genetics · 2026Review
- Mitochondrial Reactive Oxygen Species: A Unifying Mechanism in Long COVID and Spike Protein-Associated Injury: A Narrative Review.Biomolecules · 2025Review
- Novel Link Between Myeloid-Specific Adenosine Deaminase 2 and CXCL10-CXCR3 Axis in Infectious ARDS.International journal of molecular sciences · 2025Article
- A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients.Genome biology · 2025Article
- Advanced omics approaches in liver transplant settings: current applications and future prospectives.Frontiers in immunology · 2025Review
- Ferroptosis and mitochondrial ROS are central to SARS-CoV-2-induced hepatocyte death.Frontiers in cellular and infection microbiology · 2025Article
- Human vascularized macrophage-islet organoids to model immune-mediated pancreatic β cell pyroptosis upon viral infection.Cell stem cell · 2024Article
- Human Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic β cell Pyroptosis upon Viral Infection.bioRxiv : the preprint server for biology · 2024Article
- Article
- Multiplexed spatial transcriptomics methods and the application of expansion microscopy.Frontiers in cell and developmental biology · 2024Review
- Angiocrine Signaling in Sinusoidal Health and Disease.Seminars in liver disease · 2023Review
Corrections and comments
- Update of
Authors and funding
68 authors.
Yered Pita-Juarez *Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Dimitra Karagkouni *Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Nikolaos Kalavros *Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Johannes C Melms *Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA.
Sebastian Niezen *Harvard Medical School, Boston, MA, USA.
Toni M Delorey *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Adam L EsseneDepartment of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Olga R BrookDepartment of Radiology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Deepti PantDepartment of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Disha Skelton-BadlaniHarvard Medical School, Boston, MA, USA.
Pourya NaderiDepartment of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Pinzhu HuangHarvard Medical School, Boston, MA, USA.
Liuliu PanNanoString Technologies, Inc., Seattle, WA, USA.
Tyler HetherNanoString Technologies, Inc., Seattle, WA, USA.
Tallulah S AndrewsAjmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
Carly G K ZieglerHarvard Medical School, Boston, MA, USA.
Jason ReevesNanoString Technologies, Inc., Seattle, WA, USA.
Andriy MyloserdnyyHarvard Medical School, Boston, MA, USA.
Rachel ChenHarvard Medical School, Boston, MA, USA.
Andy NamNanoString Technologies, Inc., Seattle, WA, USA.
Stefan PhelanNanoString Technologies, Inc., Seattle, WA, USA.
Yan LiangNanoString Technologies, Inc., Seattle, WA, USA.
Mark GregoryNanoString Technologies, Inc., Seattle, WA, USA.
Shanshan HeNanoString Technologies, Inc., Seattle, WA, USA.
Michael PatrickNanoString Technologies, Inc., Seattle, WA, USA.
Tushar RaneNanoString Technologies, Inc., Seattle, WA, USA.
Aster WardhaniNanoString Technologies, Inc., Seattle, WA, USA.
Amit Dipak AminDepartment of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA.
Jana BiermannDepartment of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA.
Hanina HibshooshDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
Molly VereggeDepartment of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Zachary KramerDepartment of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Christopher JacobsDepartment of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Yusuf YalcinHarvard Medical School, Boston, MA, USA.
Devan PhillipsPresent Address: Genentech, 1 DNA Way, South San Francisco, CA, USA.
Michal SlyperPresent Address: Genentech, 1 DNA Way, South San Francisco, CA, USA.
Ayshwarya SubramanianKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Orr AshenbergKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Zohar Bloom-AckermannInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Victoria M TranInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
James GomezInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Alexander SturmInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Shuting ZhangInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Stephen J FlemingData Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sarah WarrenNanoString Technologies, Inc., Seattle, WA, USA.
Joseph BeechemNanoString Technologies, Inc., Seattle, WA, USA.
Deborah Hung *Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Mehrtash Babadi *Data Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Robert F Padera *Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Sonya A MacParland *Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA, USA.
Gary D Bader *Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Nasser Imad *Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Isaac H Solomon *Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Eric Miller *NanoString Technologies, Inc., Seattle, WA, USA.
Stefan Riedel *Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Caroline B M Porter *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Alexandra-Chloé Villani *Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Linus T-Y Tsai *Harvard Medical School, Boston, MA, USA.
Winston Hide *Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Gyongyi Szabo *Harvard Medical School, Boston, MA, USA.
Jonathan Hecht *Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Orit Rozenblatt-Rosen *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Alex K Shalek *Harvard Medical School, Boston, MA, USA. shalek@mit.edu.
Benjamin Izar *Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA. bi2175@cumc.columbia.edu.
Aviv Regev *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. aviv.regev.sc@gmail.com.
Yury V Popov *Harvard Medical School, Boston, MA, USA. ypopov@bidmc.harvard.edu.
Z Gordon Jiang *Harvard Medical School, Boston, MA, USA. zgjiang@bidmc.harvard.edu.
Ioannis S Vlachos *Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA. ivlachos@bidmc.harvard.edu.ORCID http://orcid.org/0000-0002-8849-808X
Funding
Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3MTransgenic CoreP30DK046200 · NIDDK · TUFTS MEDICAL CENTER · PI HU, FRANK B · 1992 to 2021
$25.0MSystems Pharmacology of Therapeutic and Adverse Responses to ImmuneCheckpoint and Small Molecule DrugsU54CA225088 · NCI · HARVARD MEDICAL SCHOOL · PI HAIGIS, MARCIA · 2018 to 2022
$10.8MOrgan Specific ProjectU54HL165440 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI HONG, YOUNG-KWON, SINGHAL, DHRUV · 2022 to 2025
$5.8MP&F programP30DK135043 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Dennis Brown · 2023 to 2026
$5.4MPrivileged and primitive hematopoietic stem cells, niches, and regulatory T cellsR01HL129506 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI FUJISAKI, JOJI · 2016 to 2025
$5.1MPan-Cancer characterization of 3’UTR somatic mutations controlling tumor immune evasionR01CA258776 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Ioannis Vlachos · 2022 to 2026
$2.9MCholesterol toxicity in alcohol-associated hepatitisR01AA030770 · NIAAA · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Zhenghui Gordon Jiang · 2023 to 2026
$2.7MMechanisms of liver metastasis and associated resistance to immunotherapyR37CA258829 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Benjamin Izar · 2021 to 2026
$2.6MMitochondrial DAMPs-driven Mechanisms of Liver Fibrosis in NASHR01DK139288 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Yury Popov · 2024 to 2026
$2.0MDissecting mechanisms of immunotherapy resistance in melanoma patientsK08CA222663 · NCI · DANA-FARBER CANCER INST · PI IZAR, BENJAMIN · 2017 to 2021
$827kBecton Dickinson LSR II Analytical Flow CytometerS10RR027050 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CLYNES, RAPHAEL A. · 2011 to 2011
$413kBill & Melinda Gates Foundation INV-027498Gates Foundation INV-027498National Blood Clot Alliance PR200524P1NCI NIH HHS K08 CA222663NCI NIH HHS K08CA222663NCI NIH HHS P30 CA013696NCI NIH HHS P30CA013696NCI NIH HHS R01 CA258776NCI NIH HHS R01 HL129506-07NCI NIH HHS R21 CA263381NCI NIH HHS R21CA263381NCI NIH HHS R37 CA258829NCI NIH HHS R37CA258829NCI NIH HHS U54 CA225088NCI NIH HHS U54CA225088NCRR NIH HHS S10 RR027050NHLBI NIH HHS R01 HL129506NHLBI NIH HHS U54 HL165440NIAAA NIH HHS R01 AA030770NIDDK NIH HHS P30 DK046200NIDDK NIH HHS P30 DK135043NIDDK NIH HHS R01 DK139288NIH Support Grant S10RR027050Office of Research Infrastructure Programs, National Institutes of Health Massachusetts Life Sciences CenterU.S. Food and Drug Administration HHSF223201810172C
Abstract
backgroundThe molecular underpinnings of organ dysfunction in severe COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we perform single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents.
resultsWe identify hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells, and a central role in a pro-fibrotic TGFβ signaling cell-cell communications network. Integrated analysis and comparisons with healthy controls reveal extensive changes in the cellular composition and expression states in COVID-19 liver, providing the underpinning of hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis characteristic of COVID-19 cholangiopathy. We also observe Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition is dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells.
conclusionsOur atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.
Indexed as
COVID-19LiverTranscriptomeAgedFemaleGene Expression ProfilingHepatocytesHumansMaleMiddle AgedSARS-CoV-2Single-Cell AnalysisCOVID-19LiverSARS-CoV-2Single-cell sequencingSingle-nucleus sequencingSpatial transcriptomics
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.