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A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients
Yered Pita-Juarez; Dimitra Karagkouni; Nikolaos Kalavros; Johannes C. Melms; Sebastian Niezen; Toni M. Delorey; Adam L Essene; Olga R. Brook; Deepti Pant; Disha Skelton-Badlani; Pourya Naderi; Pinzhu Huang; Liuliu Pan; Tyler Hether; Tallulah S. Andrews; Carly G.K. Ziegler; Jason Reeves; Andriy Myloserdnyy; Rachel Chen; Andy Nam; Stefan Phelan; Yan Liang; Amit Dipak Amin; Jana Biermann; Hanina Hibshoosh; Molly Veregge; Zachary Kramer; Christopher Jacobs; Yusuf Yalcin; Devan Phillips; Michal Slyper; Ayshwarya Subramanian; Orr Ashenberg; Zohar Bloom-Ackermann; Victoria M. Tran; James Gomez; Alexander Sturm; Shuting Zhang; Stephen J. Fleming; Sarah Warren; Joseph Beechem; Deborah Hung; Mehrtash Babadi; Gary D. Bader; Nasser Imad; Eric Miller; Stefan Riedel; Caroline B.M. Porter; Alexandra-Chloe Villani; Linus T.-Y. Tsai; Winston Hide; Gyongyi Szabo; Jonathan Hecht; Orit Rozenblatt-Rosen; Alex K. Shalek; Benjamin Izar; Aviv Regev; Yury Popov; Z. Gordon Jiang; Ioannis S. Vlachos.
Affiliation
  • Yered Pita-Juarez; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA, Harvard Medical School, Boston, MA, USA, Broad Institute of MIT and Harvard, Cam
  • Dimitra Karagkouni; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA, Harvard Medical School, Boston, MA, USA, Broad Institute of MIT and Harvard, Cam
  • Nikolaos Kalavros; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Spatial Technologies Uni
  • Johannes C. Melms; Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA, Columbia Center for Translational Immunol
  • Sebastian Niezen; Harvard Medical School, Boston, MA, USA, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA, Division of Gastroenterology, Hepatology
  • Toni M. Delorey; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Adam L Essene; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA, Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA, Division o
  • Olga R. Brook; Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA, USA
  • Deepti Pant; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA, Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA, Division o
  • Disha Skelton-Badlani; Harvard Medical School, Boston, MA, USA, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA, Division of Gastroenterology, Hepatology
  • Pourya Naderi; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA, Harvard Medical School, Boston, MA, USA
  • Pinzhu Huang; Harvard Medical School, Boston, MA, USA, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA, Division of Gastroenterology, Hepatology
  • Liuliu Pan; NanoString Technologies, Inc., Seattle, WA, USA
  • Tyler Hether; NanoString Technologies, Inc., Seattle, WA, USA
  • Tallulah S. Andrews; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada
  • Carly G.K. Ziegler; Harvard Medical School, Boston, MA, USA, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Program in Health Sciences & Technology, Harvard Medical School
  • Jason Reeves; NanoString Technologies, Inc., Seattle, WA, USA
  • Andriy Myloserdnyy; Harvard Medical School, Boston, MA, USA, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA, Division of Gastroenterology, Hepatology
  • Rachel Chen; Harvard Medical School, Boston, MA, USA, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA, Division of Gastroenterology, Hepatology
  • Andy Nam; NanoString Technologies, Inc., Seattle, WA, USA
  • Stefan Phelan; NanoString Technologies, Inc., Seattle, WA, USA
  • Yan Liang; NanoString Technologies, Inc., Seattle, WA, USA
  • Amit Dipak Amin; Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA, Columbia Center for Translational Immunol
  • Jana Biermann; Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA, Columbia Center for Translational Immunol
  • Hanina Hibshoosh; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA
  • Molly Veregge; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA, Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA, Division o
  • Zachary Kramer; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA, Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA, Division o
  • Christopher Jacobs; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA, Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA, Division o
  • Yusuf Yalcin; Harvard Medical School, Boston, MA, USA, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA, Division of Gastroenterology, Hepatology
  • Devan Phillips; Current address: Genentech, 1 DNA Way, South San Francisco, CA, USA
  • Michal Slyper; Current address: Genentech, 1 DNA Way, South San Francisco, CA, USA
  • Ayshwarya Subramanian; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Orr Ashenberg; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Zohar Bloom-Ackermann; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Victoria M. Tran; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • James Gomez; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Alexander Sturm; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Shuting Zhang; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Stephen J. Fleming; Data Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Precision Cardiology Laboratory, Broad Institute of MIT and Harvard, Cambridge,
  • Sarah Warren; NanoString Technologies, Inc., Seattle, WA, USA
  • Joseph Beechem; NanoString Technologies, Inc., Seattle, WA, USA
  • Deborah Hung; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Department of Genetics, Harvard Medical School, Boston, MA, U
  • Mehrtash Babadi; Data Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Precision Cardiology Laboratory, Broad Institute of MIT and Harvard, Cambridge,
  • Gary D. Bader; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, The Donnelly Centre, Toronto, ON, Canada
  • Nasser Imad; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
  • Eric Miller; NanoString Technologies, Inc., Seattle, WA, USA
  • Stefan Riedel; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA, Harvard Medical School, Boston, MA, USA
  • Caroline B.M. Porter; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Alexandra-Chloe Villani; Broad Institute of MIT and Harvard, Cambridge, MA, USA, Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital,
  • Linus T.-Y. Tsai; Harvard Medical School, Boston, MA, USA, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Department of Medicine, Beth Israel Deaconess Medical Center, B
  • Winston Hide; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA, Harvard Medical School, Boston, MA, USA
  • Gyongyi Szabo; Harvard Medical School, Boston, MA, USA, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Department of Medicine, Beth Israel Deaconess Medical Center, B
  • Jonathan Hecht; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA, Harvard Medical School, Boston, MA, USA
  • Orit Rozenblatt-Rosen; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Current address: Genentech, 1 DNA Way, South San Francisco, CA, USA
  • Alex K. Shalek; Harvard Medical School, Boston, MA, USA, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Program in Health Sciences & Technology, Harvard Medical School
  • Benjamin Izar; Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA, Columbia Center for Translational Immunol
  • Aviv Regev; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Current address: Genentech, 1 DNA Way, South San Francisco, CA, USA
  • Yury Popov; Harvard Medical School, Boston, MA, USA, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA, Division of Gastroenterology, Hepatology
  • Z. Gordon Jiang; Harvard Medical School, Boston, MA, USA, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA, Division of Gastroenterology, Hepatology
  • Ioannis S. Vlachos; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA, Harvard Medical School, Boston, MA, USA, Broad Institute of MIT and Harvard, Cam
Preprint in English | bioRxiv | ID: ppbiorxiv-514070
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.
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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Prognostic study Language: English Year: 2022 Document type: Preprint
Fulltext
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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Prognostic study Language: English Year: 2022 Document type: Preprint