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Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.
Muus, Christoph; Luecken, Malte D; Eraslan, Gökcen; Sikkema, Lisa; Waghray, Avinash; Heimberg, Graham; Kobayashi, Yoshihiko; Vaishnav, Eeshit Dhaval; Subramanian, Ayshwarya; Smillie, Christopher; Jagadeesh, Karthik A; Duong, Elizabeth Thu; Fiskin, Evgenij; Torlai Triglia, Elena; Ansari, Meshal; Cai, Peiwen; Lin, Brian; Buchanan, Justin; Chen, Sijia; Shu, Jian; Haber, Adam L; Chung, Hattie; Montoro, Daniel T; Adams, Taylor; Aliee, Hananeh; Allon, Samuel J; Andrusivova, Zaneta; Angelidis, Ilias; Ashenberg, Orr; Bassler, Kevin; Bécavin, Christophe; Benhar, Inbal; Bergenstråhle, Joseph; Bergenstråhle, Ludvig; Bolt, Liam; Braun, Emelie; Bui, Linh T; Callori, Steven; Chaffin, Mark; Chichelnitskiy, Evgeny; Chiou, Joshua; Conlon, Thomas M; Cuoco, Michael S; Cuomo, Anna S E; Deprez, Marie; Duclos, Grant; Fine, Denise; Fischer, David S; Ghazanfar, Shila; Gillich, Astrid.
  • Muus C; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. muus@broadinstitute.org.
  • Luecken MD; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. muus@broadinstitute.org.
  • Eraslan G; Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany. malte.luecken@helmholtz-muenchen.de.
  • Sikkema L; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Waghray A; Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.
  • Heimberg G; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Kobayashi Y; Departments of Internal Medicine and Pediatrics, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, MA, USA.
  • Vaishnav ED; Harvard Stem Cell Institute, Cambridge, MA, USA.
  • Subramanian A; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Smillie C; Department of Cell Biology, Duke University Medical School, Durham, NC, USA.
  • Jagadeesh KA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Duong ET; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Fiskin E; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Torlai Triglia E; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Ansari M; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Cai P; Division of Respiratory Medicine, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
  • Lin B; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Buchanan J; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Chen S; Comprehensive Pneumology Center (CPC)/Institute of Lung Biology and Disease (ILBD), Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
  • Shu J; Institute of Computational Biology, Helmholtz Zentrum München, Munich, Germany.
  • Haber AL; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Chung H; Departments of Internal Medicine and Pediatrics, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, MA, USA.
  • Montoro DT; Harvard Stem Cell Institute, Cambridge, MA, USA.
  • Adams T; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Aliee H; Center for Epigenomics, University of California San Diego School of Medicine, La Jolla, CA, USA.
  • Allon SJ; Department of Cellular and Molecular Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA.
  • Andrusivova Z; Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Angelidis I; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Ashenberg O; Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
  • Bassler K; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Bécavin C; Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
  • Benhar I; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Bergenstråhle J; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Bergenstråhle L; Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA.
  • Bolt L; Institute of Computational Biology, Helmholtz Zentrum München, Munich, Germany.
  • Braun E; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Bui LT; Institute for Medical Engineering and Science & Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Callori S; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Chaffin M; SciLifeLab, Department of Gene Technology, KTH Royal Institute of Technology, Stockolm, Sweden.
  • Chichelnitskiy E; Comprehensive Pneumology Center (CPC)/Institute of Lung Biology and Disease (ILBD), Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
  • Chiou J; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Conlon TM; Department for Genomics & Immunoregulation, LIMES-Institute, University of Bonn, Bonn, Germany.
  • Cuoco MS; Université Côte d'Azur, CNRS, IPMC, Sophia-Antipolis, France.
  • Cuomo ASE; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Deprez M; SciLifeLab, Department of Gene Technology, KTH Royal Institute of Technology, Stockolm, Sweden.
  • Duclos G; SciLifeLab, Department of Gene Technology, KTH Royal Institute of Technology, Stockolm, Sweden.
  • Fine D; Wellcome Sanger Institute, Hinxton, UK.
  • Fischer DS; Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
  • Ghazanfar S; Translational Genomics Research Institute, Phoenix, AZ, USA.
  • Gillich A; Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Nat Med ; 27(3): 546-559, 2021 03.
Article in English | MEDLINE | ID: covidwho-1319033
ABSTRACT
Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Sequence Analysis, RNA / Virus Internalization / Host-Pathogen Interactions / Single-Cell Analysis / SARS-CoV-2 / COVID-19 Type of study: Observational study / Prognostic study / Randomized controlled trials / Reviews Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Nat Med Journal subject: Molecular Biology / Medicine Year: 2021 Document Type: Article Affiliation country: S41591-020-01227-z

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Sequence Analysis, RNA / Virus Internalization / Host-Pathogen Interactions / Single-Cell Analysis / SARS-CoV-2 / COVID-19 Type of study: Observational study / Prognostic study / Randomized controlled trials / Reviews Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Nat Med Journal subject: Molecular Biology / Medicine Year: 2021 Document Type: Article Affiliation country: S41591-020-01227-z