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Ziegler, C.G.K.* ; Allon, S.J.* ; Nyquist, S.K.* ; Mbano, I.M.* ; Miao, V.N.* ; Tzouanas, C.N.* ; Cao, Y.* ; Yousif, A.S.* ; Bals, J.* ; Hauser, B.M.* ; Feldman, J.* ; Muus, C.* ; Wadsworth, M.H.* ; Kazer, S.W.* ; Hughes, T.K.* ; Doran, B.* ; Gatter, G.J.* ; Vukovic, M.* ; Taliaferro, F.* ; Mead, B.E.* ; Guo, Z.* ; Wang, J.P.* ; Gras, D.* ; Plaisant, M.* ; Ansari, M. ; Angelidis, I. ; Adler, H. ; Sucre, J.M.S.* ; Taylor, C.J.* ; Lin, B.* ; Waghray, A.* ; Mitsialis, V.* ; Dwyer, D.F.* ; Buchheit, K.M.* ; Boyce, J.A.* ; Barrett, N.A.* ; Laidlaw, T.M.* ; Carroll, S.L.* ; Colonna, L.* ; Tkachev, V.* ; Peterson, C.W.* ; Yu, A.* ; Zheng, H.B.* ; Gideon, H.P.* ; Winchell, C.G.* ; Lin, P.L.* ; Bingle, C.D.* ; Snapper, S.B.* ; Kropski, J.A.* ; Theis, F.J. ; Schiller, H. B. ; Zaragosi, L.E.* ; Barbry, P.* ; Leslie, A.* ; Kiem, H.P.* ; Flynn, J.L.* ; Fortune, S.M.* ; Berger, B.* ; Finberg, R.W.* ; Kean, L.S.* ; Garber, M.* ; Schmidt, A.G.* ; Lingwood, D.* ; Shalek, A.K.* ; Ordovas-Montanes, J.*

SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues.

Cell 181, 1016-1035 (2020)
Postprint Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Ace2 ; Covid-19 ; Isg ; Sars-cov-2 ; Human ; Influenza ; Interferon ; Mouse ; Non-human Primate ; Scrna-seq; Angiotensin-converting Enzyme-2; Sars Coronavirus; I Interferons; Functional Receptor; Expression; Infection; Virus; Disease; Proteins; Replication
ISSN (print) / ISBN 0092-8674
e-ISSN 1097-4172
Journal Cell
Quellenangaben Volume: 181, Issue: 5, Pages: 1016-1035 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Lung Health and Immunity (LHI)
Research Unit Lung Repair and Regeneration (LRR)
Institute of Computational Biology (ICB)