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Muus, C.* ; Luecken, M. ; Eraslan, G.* ; Sikkema, L. ; Waghray, A.* ; Heimberg, G.* ; Kobayashi, Y.* ; Vaishnav, E.D.* ; Subramanian, A.* ; Smillie, C.* ; Jagadeesh, K.A.* ; Duong, E.T.* ; Fiskin, E.* ; Triglia, E.T.* ; Ansari, M. ; Cai, P.* ; Lin, B.* ; Buchanan, J.* ; Chen, S.* ; Shu, J.* ; Haber, A.L.* ; Chung, H.* ; Montoro, D.T.* ; Adams, T.* ; Aliee, H. ; Allon, S.J.* ; Andrusivova, Z.* ; Angelidis, I. ; Ashenberg, O.* ; Bassler, K.* ; Bécavin, C.* ; Benhar, I.* ; Bergenstråhle, J.* ; Bergenstråhle, L.* ; Bolt, L.* ; Braun, E.* ; Bui, L.T.* ; Callori, S.* ; Chaffin, M.* ; Chichelnitskiy, E.* ; Chiou, J.* ; Conlon, T.M. ; Cuoco, M.S.* ; Cuomo, A.S.E.* ; Deprez, M.* ; Duclos, G.* ; Fine, D.* ; Fischer, D.S. ; Ghazanfar, S.* ; Gillich, A.* ; Giotti, B.* ; Gould, J.* ; Guo, M.* ; Gutierrez, A.J.* ; Habermann, A.C.* ; Harvey, T.* ; He, P.* ; Hou, X.* ; Hu, L.* ; Hu, Y.* ; Jaiswal, A.* ; Ji, L.* ; Jiang, P.* ; Kapellos, T.S.* ; Kuo, C.S.* ; Larsson, L.* ; Leney-Greene, M.A.* ; Lim, K.* ; Litviňuková, M.* ; Ludwig, L.S.* ; Lukassen, S.* ; Luo, W.* ; Maatz, H.* ; Madissoon, E.* ; Mamanova, L.* ; Manakongtreecheep, K.* ; Leroy, S.* ; Mayr, C. ; Mbano, I.M.* ; McAdams, A.M.* ; Nabhan, A.N.* ; Nyquist, S.K.* ; Penland, L.* ; Poirion, O.B.* ; Poli, S.* ; Qi, C.* ; Queen, R.* ; Reichart, D.* ; Rosas, I.* ; Schupp, J.C.* ; Shea, C.V.* ; Shi, X.* ; Sinha, R.* ; Sit, R.V.* ; Slowikowski, K.* ; Slyper, M.* ; Smith, N.P.* ; Sountoulidis, A.* ; Strunz, M. ; Sullivan, T.B.* ; Sun, D.* ; Talavera-López, C.* ; Tan, P.* ; Tantivit, J.* ; Travaglini, K.J.* ; Tucker, N.R.* ; Vernon, K.A.* ; Wadsworth, M.H.* ; Waldman, J.* ; Wang, X.* ; Xu, K.* ; Yan, W.* ; Zhao, W.* ; Ziegler, C.G.K.*

Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.

Nat. Med. 27, 546–559 (2021)
Postprint DOI PMC
Open Access Green
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 1078-8956
e-ISSN 1546-170X
Journal Nature medicine
Quellenangaben Volume: 27, Issue: , Pages: 546–559 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Lung Health and Immunity (LHI)
Institute of Lung Biology (LHI)
Helmholtz AI - HMGU (HAI - HMGU)
Grants German Center for Lung Research and Helmholtz Association
BHF/DZHK grant
UK Regenerative Medicine Platform
Rutherford Fund Fellowship
Netherlands Lung Foundation
MRC
Erling-Persson Family Foundation (HDCA)
Horizon2020
Swedish Foundation for Strategic Research
Erling-Persson Family Foundation (Human Developmental Cell Atlas)
Knut and Alice Wallenberg Foundation
BHF
CZI RFA CZF2019-002431e for Research Excellence
Swedish Cancer Society
Swedish Research Council
NIHR Cambridge Biomedical Research Centre
ATS Foundation/Boehringer Ingelheim Pharmaceuticals Research Fellowship in idiopathic pulmonary fibrosis
Parker B. Francis Fellowship
Manton Foundation
Klarman Cell Observatory
Cancer Research UK
Heart and Stroke Foundation
Canadian Institute of Health Research
Canada Research Chair
Richard and Susan Smith Family Foundation
Centre for Regenerative Medicine, Imperial College London
Janssen Pharmaceuticals
Stand Up to Cancer is a division of the Entertainment Industry Foundation
Stand Up to Cancer-LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational Cancer Reserach Grant
Chan Zuckerberg Initiative (CZI) Seed Network
Stanford Child Health Research Institute (Woods Family Faculty Scholarship)
European Commission (ESPACE/HEuropean Union)
European Research Council (ERC)
Medical Research Council (MRC)
Department of Defense
National Research Foundation of Korea
ERC
Doris Duke Charitable Foundation
Wall Center for Pulmonary Vascular Disease
Howard Hughes Medical Institute
Three Lakes Foundation
Federal Ministry of Education and Research of Germany in the framework of CaRNAtion
British Heart Foundation (BHF)/German Centre for Cardiovascular Research (DZHK) grant, ERC Advanced Grant under the Horizon 2020 Program
NIH award from Eunice Kennedy Shriver National Institute of Child Health and Human Development
DFG
NIH
National Institutes of Health (NIH)/NHLBI
Agence Nationale de la Recherche (France Genomique)
Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center
Rosetrees Trust
GSK
CZI Foundation
Wellcome Trust
Horizon 2020
Horizon2020 HCA 'discovAIR' project
ERC Advanced Grant under the Horizon 2020 Program
British Heart Foundation (BHF)/German Centre for Cardiovascular Research (DZHK) grant
CZI
LENDULET-BIOMAG grant
CZI Seed Network grant
Stanford Child Health Research Institute
CZI Biohub
LungMAP and CZI Seed Network
Agence Nationale de la Recherche (SAHARRA)
Agence Nationale de la Recherche (UCAJEDI)
Ministry of Economic Affairs and Climate Policy
ERC advanced grant New-Chol
CZI DAF, an advised fund of Silicon Valley Community Foundation
NIAID Novel Alternative Model Systems for Enteric Diseases consortium
HGF grant sparse2big
German Research Foundation (ImmunoSensation2-the immune sensory system)
Helmholtz Association
CPI
ATS Foundation/Boehringer Ingelheim Pharmaceuticals Research Fellowship
CZI-HCA Seed projects
NHLBI/NIH
HubMap consortium
European Commission (ESPACE/HEuropean Union Horizon 2020 Research and Innovation Program)
German Center for Lung Research
Helmholtz Association's Initiative and Networking Fund through Helmholtz AI
Silicon Valley Community Foundation
NIAID Novel Alternative Model Systems
NHLBI
Bill and Melinda Gates Foundation
Sloan Fellowship in Chemistry
Beckman Young Investigator Program
NIH (NHLBI)
HGF
German Research Foundation (DFG)
National Science Foundation
Cambridge University Hospitals NIHR Biomedical Research Centre
NHLBI Molecular Atlas of Lung Development Program Human Tissue Core grants
National Natural Science Foundation of China
National Key RD Program
Conseil Departemental des Alpes Maritimes
CZI (Silicon Valley Foundation)
Fondation pour la Recherche Medicale
Agence Nationale de la Recherche
Ministry of Economic Affairs and Climate Policy by means of the PPP
MRC of the Wellcome-MRC Cambridge Stem Cell Institute
Boehringer Ingelheim