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

  • Biology
  • Cell Atlas
  • Genomics
  • Immunology
  • Infectious Disease
  • Statistics
  • Carly Ziegler
  • Sam Allon
  • Sarah Nyquist
  • Vincent Miao
  • Constantine Tzouanas
  • Marc Wadsworth II
  • Sam Kazer
  • Travis Hughes
  • Benjamin Doran
  • James Gatter
  • Marko Vukovic
  • Ben Mead
  • Shaina Carroll
  • Alex K. Shalek
  • José Ordovas-Montañes
  • Ziegler et al.▾
    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 II, 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.#, HCA Lung Biological Network
  • Cell
  • April, 2020
Biology
Cell Atlas
Genomics
Immunology
Infectious Disease
Statistics
Carly Ziegler
Sam Allon
Sarah Nyquist
Vincent Miao
Constantine Tzouanas
Marc Wadsworth II
Sam Kazer
Travis Hughes
Benjamin Doran
James Gatter
Marko Vukovic
Ben Mead
Shaina Carroll
Alex K. Shalek
José Ordovas-Montañes

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. SARS-CoV- 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 species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.

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