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SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.

Publication ,  Journal Article
Ziegler, CGK; Allon, SJ; Nyquist, SK; Mbano, IM; Miao, VN; Tzouanas, CN; Cao, Y; Yousif, AS; Bals, J; Hauser, BM; Feldman, J; Muus, C; Guo, Z ...
Published in: Cell
May 28, 2020

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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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

May 28, 2020

Volume

181

Issue

5

Start / End Page

1016 / 1035.e19

Location

United States

Related Subject Headings

  • Up-Regulation
  • Tuberculosis
  • Single-Cell Analysis
  • Serine Endopeptidases
  • SARS-CoV-2
  • Receptors, Virus
  • Pneumonia, Viral
  • Peptidyl-Dipeptidase A
  • Pandemics
  • Nasal Mucosa
 

Citation

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Ziegler, C. G. K., Allon, S. J., Nyquist, S. K., Mbano, I. M., Miao, V. N., Tzouanas, C. N., … HCA Lung Biological Network, . (2020). 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(5), 1016-1035.e19. https://doi.org/10.1016/j.cell.2020.04.035
Ziegler, Carly G. K., Samuel J. Allon, Sarah K. Nyquist, Ian M. Mbano, Vincent N. Miao, Constantine N. Tzouanas, Yuming Cao, 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 181, no. 5 (May 28, 2020): 1016-1035.e19. https://doi.org/10.1016/j.cell.2020.04.035.
Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN, 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. 2020 May 28;181(5):1016-1035.e19.
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, vol. 181, no. 5, May 2020, pp. 1016-1035.e19. Pubmed, doi:10.1016/j.cell.2020.04.035.
Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN, Cao Y, Yousif AS, Bals J, Hauser BM, Feldman J, Muus C, Wadsworth MH, Kazer SW, Hughes TK, Doran B, Gatter GJ, Vukovic M, Taliaferro F, Mead BE, Guo Z, Wang JP, Gras D, Plaisant M, Ansari M, Angelidis I, Adler H, Sucre JMS, Taylor CJ, Lin B, Waghray A, Mitsialis V, Dwyer DF, Buchheit KM, Boyce JA, Barrett NA, Laidlaw TM, Carroll SL, Colonna L, Tkachev V, Peterson CW, Yu A, Zheng HB, Gideon HP, Winchell CG, Lin PL, Bingle CD, Snapper SB, Kropski JA, Theis FJ, Schiller HB, Zaragosi L-E, Barbry P, Leslie A, Kiem H-P, Flynn JL, Fortune SM, Berger B, Finberg RW, Kean LS, Garber M, Schmidt AG, Lingwood D, Shalek AK, Ordovas-Montanes J, HCA Lung Biological Network. Electronic address: lung-network@humancellatlas.org, HCA Lung Biological Network. 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. 2020 May 28;181(5):1016-1035.e19.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

May 28, 2020

Volume

181

Issue

5

Start / End Page

1016 / 1035.e19

Location

United States

Related Subject Headings

  • Up-Regulation
  • Tuberculosis
  • Single-Cell Analysis
  • Serine Endopeptidases
  • SARS-CoV-2
  • Receptors, Virus
  • Pneumonia, Viral
  • Peptidyl-Dipeptidase A
  • Pandemics
  • Nasal Mucosa