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Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells
Christoph Muus; Malte D Luecken; Gokcen Eraslan; Avinash Waghray; Graham Heimberg; Lisa Sikkema; Yoshihiko Kobayashi; Eeshit Dhaval Vaishnav; Ayshwarya Subramanian; Christopher Smillie; Karthik Jagadeesh; Elizabeth Thu Duong; Evgenij Fiskin; Elena Torlai Triglia; Christophe Becavin; Meshal Ansari; Peiwen Cai; Brian Lin; Justin Buchanan; Jian Shu; Adam L Haber; Hattie Chung; Daniel T Montoro; Taylor Adams; Hananeh Aliee; Samuel J Allon; Zaneta Andrusivova; Ilias Angelidis; Orr Ashenberg; Kevin Bassler; Inbal Benhar; Joseph Bergenstrahle; Ludvig Bergenstrahle; Liam Bolt; Emelie Braun; Linh T Bui; Mark Chaffin; Evgeny Chichelnitskiy; Joshua Chiou; Thomas M Conlon; Michael S Cuoco; Marie Deprez; David S Fischer; Astrid Gillich; Joshua Gould; Austin J Gutierrez; Arun C Habermann; Tyler Harvey; Peng He; Xiaomeng Hou; Lijuan Hu; Alok Jaiswal; Peiyong Jiang; Theodoros Kapellos; Christin S Kuo; Ludvig Larsson; Michael A Leney-Greene; Kyungtae Lim; Monika Litvinukova; Ji Lu; Leif S Ludwig; Wendy Luo; Henrike Maatz; Elo Maddissoon; Lira Mamanova; Kasidet Manakongtreecheep; Ian Mbano; Alexi M McAdams; Ross J Metzger; Ahmad N Nabhan; Sarah K Nyquist; Jose Ordovas-Montanes; Lolita Penland; Olivier B Poirion; Segio Poli; CanCan Qi; Daniel Reichart; Ivan Rosas; Jonas Schupp; Rahul Sinha; Rene V Sit; Kamil Slowikowski; Michal Slyper; Neal Smith; Alex Sountoulidis; Maximilian Strunz; Dawei Sun; Carlos Talavera-Lopez; Peng Tan; Jessica Tantivit; Kyle J Travaglini; Nathan R Tucker; Katherine Vernon; Marc H Wadsworth III; Julia Waldman; Xiuting Wang; Wenjun Yan; Ali Onder Yildirim; William Zhao; Carly G K Ziegler; Aviv Regev; - The NHLBI LungMAP Consortium; - The Human Cell Atlas Lung Biological Network.
Afiliación
  • Christoph Muus; Broad Institute
  • Malte D Luecken; Institute of Computational Biology, Helmholtz Zentrum Munchen, Munich, Germany
  • Gokcen Eraslan; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Avinash Waghray; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA Departments of Internal Medicine and Pediatrics, Pulmonary and Critical Care U
  • Graham Heimberg; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Lisa Sikkema; Institute of Computational Biology, Helmholtz Zentrum Munchen, Munich, Germany
  • Yoshihiko Kobayashi; Department of Cell Biology, Duke University Medical School, Durham, NC 27710, USA
  • Eeshit Dhaval Vaishnav; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA Department of Biology, Massachusetts Institute of Technology, Cambridge,
  • Ayshwarya Subramanian; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Christopher Smillie; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Karthik Jagadeesh; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Elizabeth Thu Duong; University of California San Diego Department of Pediatrics, Division of Respiratory Medicine
  • Evgenij Fiskin; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Elena Torlai Triglia; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Christophe Becavin; Universite Cote dAzur, CNRS, IPMC, Sophia-Antipolis, 06560, France
  • Meshal Ansari; Comprehensive Pneumology Center (CPC) / Institute of Lung Biology and Disease (ILBD), Helmholtz Zentrum Munchen, Member of the German Center for Lung Research (
  • Peiwen Cai; Department of Genetics and Genomic Sciences, Icahn School of Medicineat Mount Sinai, New York, NY 10029, USA
  • Brian Lin; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA Departments of Internal Medicine and Pediatrics, Pulmonary and Critical Care U
  • Justin Buchanan; Center for Epigenomics, University of California-San Diego School of Medicine, La Jolla, CA, 92093. Department of Cellular and Molecular Medicine, University of
  • Jian Shu; Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA Whitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA
  • Adam L Haber; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA. Klarman Cell Observatory, Broad Institute of MIT and Harv
  • Hattie Chung; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Daniel T Montoro; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Taylor Adams; Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine
  • Hananeh Aliee; Institute of Computational Biology, Helmholtz Zentrum Munchen, Member of the German Center for Lung Research (DZL), Munich, Germany
  • Samuel J Allon; Institute for Medical Engineering and Science & Department of Chemistry, MIT; Ragon Institute of MGH, MIT and Harvard; Broad Institute of MIT and Harvard
  • Zaneta Andrusivova; SciLifeLab, Department of Gene Technology, KTH Royal Institute of Technology
  • Ilias Angelidis; Comprehensive Pneumology Center (CPC) / Institute of Lung Biology and Disease (ILBD), Helmholtz Zentrum Munchen, Member of the German Center for Lung Research (
  • Orr Ashenberg; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Kevin Bassler; Department for Genomics & Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany
  • Inbal Benhar; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA Center for Brain Science, Harvard University, Cambridge, MA 02138 Depart
  • Joseph Bergenstrahle; SciLifeLab, Department of Gene Technology, KTH Royal Institute of Technology
  • Ludvig Bergenstrahle; SciLifeLab, Department of Gene Technology, KTH Royal Institute of Technology
  • Liam Bolt; Wellcome Sanger Institute, Hinxton, Cambridgeshire, CB10 1SA, UK
  • Emelie Braun; Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute
  • Linh T Bui; Translational Genomics Research Institute, Phoenix, AZ
  • Mark Chaffin; Precision Cardiology Laboratory, The Broad Institute, Cambridge, MA, USA 02142
  • Evgeny Chichelnitskiy; Institute of Transplant Immunology, Hannover Medical School, MHH, Carl-Neuberg Str. 1, 30625 Hannover, Germany, phone +40 511 532 9745; fax +40 511 532 8090; Ge
  • Joshua Chiou; Biomedical Sciences Graduate Program, University of California-San Diego, La Jolla, CA, 92093
  • Thomas M Conlon; Comprehensive Pneumology Center (CPC) / Institute of Lung Biology and Disease (ILBD), Helmholtz Zentrum Munchen, Member of the German Center for Lung Research (
  • Michael S Cuoco; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Marie Deprez; Universite Cote dAzur, CNRS, IPMC, Sophia-Antipolis, 06560, France
  • David S Fischer; Institute of Computational Biology, Helmholtz Zentrum Munchen, Munich, Germany
  • Astrid Gillich; Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA.
  • Joshua Gould; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Austin J Gutierrez; Translational Genomics Research Institute, Phoenix, AZ
  • Arun C Habermann; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
  • Tyler Harvey; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Peng He; Wellcome Sanger Institute, Hinxton, Cambridgeshire, CB10 1SA, UK
  • Xiaomeng Hou; Center for Epigenomics, University of California-San Diego School of Medicine, La Jolla, CA, 92093. Department of Cellular and Molecular Medicine, University of
  • Lijuan Hu; Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute
  • Alok Jaiswal; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Peiyong Jiang; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China
  • Theodoros Kapellos; Department for Genomics & Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany
  • Christin S Kuo; Department of Pediatrics, Pulmonary Medicine, Stanford University School of Medicine, Stanford, CA.
  • Ludvig Larsson; SciLifeLab, Department of Gene Technology, KTH Royal Institute of Technology
  • Michael A Leney-Greene; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Kyungtae Lim; Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, UK
  • Monika Litvinukova; Cellular Genetics Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.; Cardiovascular and Metabolic Scien
  • Ji Lu; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China
  • Leif S Ludwig; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA Division of Hematology / Oncology, Boston Childrens Hospital and Departm
  • Wendy Luo; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Henrike Maatz; Cardiovascular and Metabolic Sciences, Max Delbruck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
  • Elo Maddissoon; Wellcome Sanger Institute, Hinxton, Cambridgeshire, CB10 1SA, UK
  • Lira Mamanova; Wellcome Sanger Institute, Hinxton, Cambridgeshire, CB10 1SA, UK
  • Kasidet Manakongtreecheep; Broad Institute of MIT and Harvard, Cambridge, MA, USA Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA Cente
  • Ian Mbano; Africa Health Research Institute, Durban, South Africa
  • Alexi M McAdams; Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear, Boston, MA 02114
  • Ross J Metzger; Vera Moulton Wall Center for Pulmonary Vascular Disease, Department of Pediatrics, Division of Cardiology, Stanford University School of Medicine, Stanford, CA
  • Ahmad N Nabhan; Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA.
  • Sarah K Nyquist; Computational and Systems Biology, CSAIL, Institute for Medical Engineering and Science & Department of Chemistry, MIT; Ragon Institute of MGH, MIT and Harvard;
  • Jose Ordovas-Montanes; Division of Gastroenterology Boston Childrens Hospital; Program in Immunology Harvard Medical School; Harvard Stem Cell Institute; Broad Institute of MIT and Ha
  • Lolita Penland; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Olivier B Poirion; Center for Epigenomics, University of California-San Diego School of Medicine, La Jolla, CA, 92093. Department of Cellular and Molecular Medicine, University of
  • Segio Poli; Division of Internal Medicine - Mount Sinai Medical Center, Miami Beach, FL
  • CanCan Qi; Dept. of Pediatric Pulmonology and Pediatric Allergology, Beatrix Childrens Hospital, University of Groningen, University Medical Center Groningen, Groningen, T
  • Daniel Reichart; Department of Genetics, Harvard Medical School, Boston, MA, United States.; Department of Cardiology, University Heart&Vascular Center, University of Hamburg, H
  • Ivan Rosas; Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine
  • Jonas Schupp; Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine
  • Rahul Sinha; Institute for Stem Cell Biology and Regenerative Medicine, Department of Pathology, Stanford University School of Medicine, Stanford, CA
  • Rene V Sit; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Kamil Slowikowski; Broad Institute of MIT and Harvard, Cambridge, MA, USA Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA Cente
  • Michal Slyper; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Neal Smith; Broad Institute of MIT and Harvard, Cambridge, MA, USA Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA Cente
  • Alex Sountoulidis; Stockholm University, Department of Molecular Biosciences, The Wenner-Gren Institute
  • Maximilian Strunz; Comprehensive Pneumology Center (CPC) / Institute of Lung Biology and Disease (ILBD), Helmholtz Zentrum Munchen, Member of the German Center for Lung Research (
  • Dawei Sun; Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, UK
  • Carlos Talavera-Lopez; Cellular Genetics Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom
  • Peng Tan; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Jessica Tantivit; Broad Institute of MIT and Harvard, Cambridge, MA, USA Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA Cente
  • Kyle J Travaglini; Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA.
  • Nathan R Tucker; Precision Cardiology Laboratory, The Broad Institute, Cambridge, MA, USA 02142 Masonic Medical Research Institute, Utica, NY, USA 13501
  • Katherine Vernon; Department of Medicine, Brigham and Womens Hospital and Harvard Medical School, Boston, MA, USA Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Marc H Wadsworth III; Institute for Medical Engineering and Science, Department of Chemistry & Koch Institute for Integrative Cancer Research, MIT; Ragon Institute of MGH, MIT and Ha
  • Julia Waldman; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
  • Xiuting Wang; Department of Genetics and Genomic Sciences, Icahn School of Medicineat Mount Sinai, New York, NY 10029, USA
  • Wenjun Yan; Center for Brain Science, Harvard University, Cambridge, MA 02138 Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138
  • Ali Onder Yildirim; Comprehensive Pneumology Center (CPC) / Institute of Lung Biology and Disease (ILBD), Helmholtz Zentrum Munchen, Member of the German Center for Lung Research (
  • William Zhao; Department of Genetics and Genomic Sciences, Icahn School of Medicineat Mount Sinai, New York, NY 10029, USA
  • Carly G K Ziegler; Harvard-MIT Health Sciences and Technology, Institute for Medical Engineering and Science, Koch Institute for Integrative Cancer Research, MIT; Broad Institute
  • Aviv Regev; MIT and Broad Inst. of MIT & Harvard
  • - The NHLBI LungMAP Consortium; -
  • - The Human Cell Atlas Lung Biological Network; -
Preprint en En | PREPRINT-BIORXIV | ID: ppbiorxiv-049254
ABSTRACT
The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been associated with COVID-19 transmission or pathology, including gut enterocytes, corneal epithelial cells, cardiomyocytes, heart pericytes, olfactory sustentacular cells, and renal epithelial cells. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. Notably, there was a particularly low expression of ACE2 in the few young pediatric samples in the analysis. Further analysis reveals a gene expression program shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues, including genes that may mediate viral entry, subtend key immune functions, and mediate epithelial-macrophage cross-talk. Amongst these are IL6, its receptor and co-receptor, IL1R, TNF response pathways, and complement genes. Cell type specificity in the lung and airways and smoking effects were conserved in mice. Our analyses suggest that differences in the cell type-specific expression of mediators of SARS-CoV-2 viral entry may be responsible for aspects of COVID-19 epidemiology and clinical course, and point to putative molecular pathways involved in disease susceptibility and pathogenesis.
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Experimental_studies / Prognostic_studies / Rct / Review Idioma: En Año: 2020 Tipo del documento: Preprint
Texto completo
Añadir a Mi BVS
Imprimir
XML
Buscar en Google
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Experimental_studies / Prognostic_studies / Rct / Review Idioma: En Año: 2020 Tipo del documento: Preprint