TY - JOUR AU - Ziegler, Carly G. K. AU - Allon, Samuel J. AU - Nyquist, Sarah K. AU - Mbano, Ian M. AU - Miao, Vincent N. AU - Tzouanas, Constantine N. AU - Cao, Yuming AU - Yousif, Ashraf S. AU - Bals, Julia AU - Hauser, Blake M. AU - Feldman, Jared AU - Muus, Christoph AU - Wadsworth, Marc H. II AU - Kazer, Samuel W. AU - Hughes, Travis K. AU - Doran, Benjamin AU - Gatter, G. James AU - Vukovic, Marko AU - Taliaferro, Faith AU - Mead, Benjamin E. AU - Guo, Zhiru AU - Wang, Jennifer P. AU - Gras, Delphine AU - Plaisant, Magali AU - Ansari, Meshal AU - Angelidis, Ilias AU - Adler, Heiko AU - Sucre, Jennifer M. S. AU - Taylor, Chase J. AU - Lin, Brian AU - Waghray, Avinash AU - Mitsialis, Vanessa AU - Dwyer, Daniel F. AU - Buchheit, Kathleen M. AU - Boyce, Joshua A. AU - Barrett, Nora A. AU - Laidlaw, Tanya M. AU - Carroll, Shaina L. AU - Colonna, Lucrezia AU - Tkachev, Victor AU - Peterson, Christopher W. AU - Yu, Alison AU - Zheng, Hengqi Betty AU - Gideon, Hannah P. AU - Winchell, Caylin G. AU - Lin, Philana Ling AU - Bingle, Colin D. AU - Snapper, Scott B. AU - Kropski, Jonathan A. AU - Theis, Fabian J. AU - Schiller, Herbert B. AU - Zaragosi, Laure-Emmanuelle AU - Barbry, Pascal AU - Leslie, Alasdair AU - Kiem, Hans-Peter AU - Flynn, JoAnne L. AU - Fortune, Sarah M. AU - Berger, Bonnie AU - Finberg, Robert W. AU - Kean, Leslie S. AU - Garber, Manuel AU - Schmidt, Aaron G. AU - Lingwood, Daniel AU - Shalek, Alex K. AU - Ordovas-Montanes, Jose ED - Horváth, Péter / Collaborator TI - SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues JF - CELL J2 - CELL VL - 181 PY - 2020 IS - 5 SP - 1016 EP - 1035 PG - 20 SN - 0092-8674 DO - 10.1016/j.cell.2020.04.035 UR - https://m2.mtmt.hu/api/publication/31598355 ID - 31598355 N1 - Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA 02115, United States Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, United States Broad Institute of MIT and Harvard, Cambridge, MA 02142, United States Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA 02138, United States Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Program in Computational & Systems Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Computer Science & Artificial Intelligence Lab, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Africa Health Research Institute, Durban, South Africa School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa University of Massachusetts Medical School, Worcester, MA 01655, United States Department of Microbiology, Harvard Medical School, Boston, MA 02115, United States Program in Virology, Harvard Medical School, Boston, MA 02115, United States John A. Paulson School of Engineering & Applied Sciences, Harvard University, Cambridge, MA 02138, United States Program in Immunology, Harvard Medical School, Boston, MA 02115, United States Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, United States Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA 02115, United States Aix-Marseille University, INSERM, INRA, C2VN, Marseille, France Université, Côte d'Azur, CNRS, IPMC, Sophia-Antipolis, France Comprehensive Pneumology Center & Institute of Lung Biology and Disease, Helmholtz Zentrum München, Munich, Germany German Center for Lung Research, Munich, Germany Institute of Computational Biology, Helmholtz Zentrum München, Munich, Germany Research Unit Lung Repair and Regeneration, Helmholtz Zentrum München, Munich, Germany Division of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, United States Divison of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, United States Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, United States Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA 02115, United States Division of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, United States University of California, Berkeley, CA 94720, United States University of Washington, Seattle, WA 98195, United States Dana Farber Cancer Institute, Boston, MA 02115, United States Harvard Medical School, Boston, MA 02115, United States Stem Cell & Gene Therapy Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States Department of Medicine, University of Washington, Seattle, WA 98195, United States Division of Gastroenterology and Hepatology, Seattle Children's Hospital, Seattle, WA 98145, United States Department of Microbiology & Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, United States Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United States Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, United States Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, United States Department of Infection, Immunity & Cardiovascular Disease, The Medical School and The Florey Institute for Host Pathogen Interactions, University of Sheffield, Sheffield, S10 2TN, United Kingdom Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, United States Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37240, United States Department of Veterans Affairs Medical Center, Nashville, TN 37212, United States Department of Infection & Immunity, University College London, London, United Kingdom Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Harvard Stem Cell Institute, Cambridge, MA 02138, United States Cited By :144 Export Date: 16 September 2020 CODEN: CELLB Correspondence Address: Shalek, A.K.; Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Broad Institute of MIT and HarvardUnited States; email: shalek@mit.edu Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA 02115, United States Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, United States Broad Institute of MIT and Harvard, Cambridge, MA 02142, United States Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA 02138, United States Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Program in Computational & Systems Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Computer Science & Artificial Intelligence Lab, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Africa Health Research Institute, Durban, South Africa School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa University of Massachusetts Medical School, Worcester, MA 01655, United States Department of Microbiology, Harvard Medical School, Boston, MA 02115, United States Program in Virology, Harvard Medical School, Boston, MA 02115, United States John A. Paulson School of Engineering & Applied Sciences, Harvard University, Cambridge, MA 02138, United States Program in Immunology, Harvard Medical School, Boston, MA 02115, United States Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, United States Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA 02115, United States Aix-Marseille University, INSERM, INRA, C2VN, Marseille, France Université, Côte d'Azur, CNRS, IPMC, Sophia-Antipolis, France Comprehensive Pneumology Center & Institute of Lung Biology and Disease, Helmholtz Zentrum München, Munich, Germany German Center for Lung Research, Munich, Germany Institute of Computational Biology, Helmholtz Zentrum München, Munich, Germany Research Unit Lung Repair and Regeneration, Helmholtz Zentrum München, Munich, Germany Division of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, United States Divison of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, United States Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, United States Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA 02115, United States Division of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, United States University of California, Berkeley, CA 94720, United States University of Washington, Seattle, WA 98195, United States Dana Farber Cancer Institute, Boston, MA 02115, United States Harvard Medical School, Boston, MA 02115, United States Stem Cell & Gene Therapy Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States Department of Medicine, University of Washington, Seattle, WA 98195, United States Division of Gastroenterology and Hepatology, Seattle Children's Hospital, Seattle, WA 98145, United States Department of Microbiology & Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, United States Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United States Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, United States Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, United States Department of Infection, Immunity & Cardiovascular Disease, The Medical School and The Florey Institute for Host Pathogen Interactions, University of Sheffield, Sheffield, S10 2TN, United Kingdom Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, United States Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37240, United States Department of Veterans Affairs Medical Center, Nashville, TN 37212, United States Department of Infection & Immunity, University College London, London, United Kingdom Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Harvard Stem Cell Institute, Cambridge, MA 02138, United States Cited By :542 Export Date: 22 April 2021 CODEN: CELLB Correspondence Address: Shalek, A.K.; Program in Health Sciences & Technology, United States; email: shalek@mit.edu Correspondence Address: Ordovas-Montanes, J.; Broad Institute of MIT and HarvardUnited States; email: jose.ordovas-montanes@childrens.harvard.edu AB - There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection. LA - English DB - MTMT ER -