SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues
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Author(s)
Ziegler, Carly G.K.
Allon, Samuel J.
Nyquist, Sarah K.
Mbano, Ian M.
Miao, Vincent N.
Tzouanas, Constantine N.
Cao, Yuming
Yousif, Ashraf S.
Bals, Julia
Hauser, Blake M.
Date Issued
April 2020
Journal
Cell
Publisher
Elsevier BV
Citation
Ziegler, Carly G.K. et al. "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 (April 2020): 11384 © 2020 Elsevier
Version
Final published version
Abstract
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. SARSCoV-
2 spike (S)-protein binds ACE2, and in concert with host proteases, principally 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 amongst 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 discover 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 speciesspecific
interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury,
to enhance infection.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cell.2020.04.035
