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DOI 10.1016/j.cell.2020.04.035

Медицинская библиотека · Cell · 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.

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, Feldman Jared, Muus Christoph, Wadsworth Marc H, Kazer Samuel W, Hughes Travis K, Doran Benjamin, Gatter G James, Vukovic Marko, Taliaferro Faith, Mead Benjamin E, Guo Zhiru, Wang Jennifer P, Gras Delphine, Plaisant Magali, Ansari Meshal, Angelidis Ilias, Adler Heiko, Sucre Jennifer M S, Taylor Chase J, Lin Brian, Waghray Avinash, Mitsialis Vanessa, Dwyer Daniel F, Buchheit Kathleen M, Boyce Joshua A, Barrett Nora A, Laidlaw Tanya M, Carroll Shaina L, Colonna Lucrezia, Tkachev Victor, Peterson Christopher W, Yu Alison, Zheng Hengqi Betty, Gideon Hannah P, Winchell Caylin G, Lin Philana Ling, Bingle Colin D, Snapper Scott B, Kropski Jonathan A, Theis Fabian J, Schiller Herbert B, Zaragosi Laure-Emmanuelle, Barbry Pascal, Leslie Alasdair, Kiem Hans-Peter, Flynn JoAnne L, Fortune Sarah M, Berger Bonnie, Finberg Robert W, Kean Leslie S, Garber Manuel, Schmidt Aaron G, Lingwood Daniel, Shalek Alex K, Ordovas-Montanes Jose, HCA Lung Biological Network. Electronic address: lung-network@humancellatlas.org, HCA Lung Biological Network

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод пока не подготовлен

Аннотация

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.

Для цитирования: 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, Feldman Jared, Muus Christoph, Wadsworth Marc H, Kazer Samuel W, Hughes Travis K, Doran Benjamin, Gatter G James, Vukovic Marko, Taliaferro Faith, Mead Benjamin E, Guo Zhiru, Wang Jennifer P, Gras Delphine, Plaisant Magali, Ansari Meshal, Angelidis Ilias, Adler Heiko, Sucre Jennifer M S, Taylor Chase J, Lin Brian, Waghray Avinash, Mitsialis Vanessa, Dwyer Daniel F, Buchheit Kathleen M, Boyce Joshua A, Barrett Nora A, Laidlaw Tanya M, Carroll Shaina L, Colonna Lucrezia, Tkachev Victor, Peterson Christopher W, Yu Alison, Zheng Hengqi Betty, Gideon Hannah P, Winchell Caylin G, Lin Philana Ling, Bingle Colin D, Snapper Scott B, Kropski Jonathan A, Theis Fabian J, Schiller Herbert B, Zaragosi Laure-Emmanuelle, Barbry Pascal, Leslie Alasdair, Kiem Hans-Peter, Flynn JoAnne L, Fortune Sarah M, Berger Bonnie, Finberg Robert W, Kean Leslie S, Garber Manuel, Schmidt Aaron G, Lingwood Daniel, Shalek Alex K, Ordovas-Montanes Jose, 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. DOI: 10.1016/j.cell.2020.04.035.

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