Plate IV.322 · Publications
SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues
Article in Cell, May 2020.
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 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.
Cite
@article{ziegler2020sars,
title = {{SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues}},
author = {Ziegler, Carly G.K. and Allon, Samuel J. and Nyquist, Sarah K. and Mbano, Ian M. and Miao, Vincent N. and Tzouanas, Constantine N. and Cao, Yuming and Yousif, Ashraf S. and Bals, Julia and Hauser, Blake M. and Feldman, Jared and Muus, Christoph and Wadsworth, Marc H. and Kazer, Samuel W. and Hughes, Travis K. and Doran, Benjamin and Gatter, G. James and Vukovic, Marko and Taliaferro, Faith and Mead, Benjamin E. and Guo, Zhiru and Wang, Jennifer P. and Gras, Delphine and Plaisant, Magali and Ansari, Meshal and Angelidis, Ilias and Adler, Heiko and Sucre, Jennifer M.S. and Taylor, Chase J. and Lin, Brian and Waghray, Avinash and Mitsialis, Vanessa and Dwyer, Daniel F. and Buchheit, Kathleen M. and Boyce, Joshua A. and Barrett, Nora A. and Laidlaw, Tanya M. and Carroll, Shaina L. and Colonna, Lucrezia and Tkachev, Victor and Peterson, Christopher W. and Yu, Alison and Zheng, Hengqi Betty and Gideon, Hannah P. and Winchell, Caylin G. and Lin, Philana Ling and Bingle, Colin D. and Snapper, Scott B. and Kropski, Jonathan A. and Theis, Fabian J. and Schiller, Herbert B. and Zaragosi, Laure-Emmanuelle and Barbry, Pascal and Leslie, Alasdair and Kiem, Hans-Peter and Flynn, JoAnne L. and Fortune, Sarah M. and Berger, Bonnie and Finberg, Robert W. and Kean, Leslie S. and Garber, Manuel and Schmidt, Aaron G. and Lingwood, Daniel and Shalek, Alex K. and Ordovas-Montanes, Jose and Banovich, Nicholas and Barbry, Pascal and Brazma, Alvis and Desai, Tushar and Duong, Thu Elizabeth and Eickelberg, Oliver and Falk, Christine and Farzan, Michael and Glass, Ian and Haniffa, Muzlifah and Horvath, Peter and Hung, Deborah and Kaminski, Naftali and Krasnow, Mark and Kropski, Jonathan A. and Kuhnemund, Malte and Lafyatis, Robert and Lee, Haeock and Leroy, Sylvie and Linnarson, Sten and Lundeberg, Joakim and Meyer, Kerstin and Misharin, Alexander and Nawijn, Martijn and Nikolic, Marko Z. and Ordovas-Montanes, Jose and Pe’er, Dana and Powell, Joseph and Quake, Stephen and Rajagopal, Jay and Tata, Purushothama Rao and Rawlins, Emma L. and Regev, Aviv and Reyfman, Paul A. and Rojas, Mauricio and Rosen, Orit and Saeb-Parsy, Kourosh and Samakovlis, Christos and Schiller, Herbert and Schultze, Joachim L. and Seibold, Max A. and Shalek, Alex K. and Shepherd, Douglas and Spence, Jason and Spira, Avrum and Sun, Xin and Teichmann, Sarah and Theis, Fabian and Tsankov, Alexander and van den Berge, Maarten and von Papen, Michael and Whitsett, Jeffrey and Xavier, Ramnik and Xu, Yan and Zaragosi, Laure-Emmanuelle and Zhang, Kun},
journal = {Cell},
publisher = {Elsevier BV},
year = {2020},
month = may,
doi = {10.1016/j.cell.2020.04.035},
url = {https://doi.org/10.1016/j.cell.2020.04.035},
pmid = {32413319},
pmcid = {PMC7252096}
}