• Ziegler Carly G K CGK Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA 02115, USA; Institute for Medica, Samuel J Allon, Sarah K Nyquist, Ian M Mbano, Vincent N Miao, Constantine N Tzouanas, Yuming Cao, Ashraf S Yousif, Julia Bals, Blake M Hauser, Jared Feldman, Christoph Muus, Marc H Wadsworth, Samuel W Kazer, Travis K Hughes, Benjamin Doran, G James Gatter, Marko Vukovic, Faith Taliaferro, Benjamin E Mead, Zhiru Guo, Jennifer P Wang, Delphine Gras, Magali Plaisant, Meshal Ansari, Ilias Angelidis, Heiko Adler, Jennifer M S Sucre, Chase J Taylor, Brian Lin, Avinash Waghray, Vanessa Mitsialis, Daniel F Dwyer, Kathleen M Buchheit, Joshua A Boyce, Nora A Barrett, Tanya M Laidlaw, Shaina L Carroll, Lucrezia Colonna, Victor Tkachev, Christopher W Peterson, Alison Yu, Hengqi Betty Zheng, Hannah P Gideon, Caylin G Winchell, Philana Ling Lin, Colin D Bingle, Scott B Snapper, Jonathan A Kropski, Fabian J Theis, Herbert B Schiller, Laure-Emmanuelle Zaragosi, Pascal Barbry, Alasdair Leslie, Hans-Peter Kiem, JoAnne L Flynn, Sarah M Fortune, Bonnie Berger, Robert W Finberg, Leslie S Kean, Manuel Garber, Aaron G Schmidt, Daniel Lingwood, Alex K Shalek, Jose Ordovas-Montanes, HCA Lung Biological Network. Electronic address: lung-network@humancellatlas.org, and HCA Lung Biological Network.
• Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA 02115, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA 02138, USA.
• Cell. 2020 May 28; 181 (5): 1016-1035.e19.

AbstractThere 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.Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

66 keywords...

hide…