SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues
Authors: Philana Ling Lin
Christine Falk
Max A Seibold
Samuel W Kazer
Joakim Lundeberg
Mark Krasnow
Brian Lin
Stephen Quake
Vincent N Miao
Muzlifah Haniffa
Kathleen M Buchheit
Jared Feldman
Blake M Hauser
Chase J Taylor
Jonathan A Kropski
Douglas Shepherd
Ian M Mbano
Yuming Cao
Leslie S Kean
Christopher W Peterson
Laure-Emmanuelle Zaragosi
Dana Pe&#x27;er
Ian Glass
Alex K Shalek
Jose Ordovas-Montanes
Maarten van den Berge
Marko Vukovic
Sarah M Fortune
HCA Lung Biological Network. Electronic address: lung-network@humancellatlas.org
Oliver Eickelberg
Sarah K Nyquist
Fabian J Theis
Faith Taliaferro
Purushothama Rao Tata
Colin D Bingle
Julia Bals
Magali Plaisant
Yan Xu
Deborah Hung
Kun Zhang
Malte Kuhnemund
Tanya M Laidlaw
Samuel J Allon
Sten Linnarson
Heiko Adler
Hans-Peter Kiem
Orit Rosen
Mauricio Rojas
Alvis Brazma
Hannah P Gideon
Avinash Waghray
Vanessa Mitsialis
Marko Z Nikolic
Xin Sun
Fabian Theis
Joachim L Schultze
Delphine Gras
Ashraf S Yousif
Sarah Teichmann
Joshua A Boyce
Kourosh Saeb-Parsy
Alasdair Leslie
Victor Tkachev
Paul A Reyfman
Nora A Barrett
Jason Spence
Caylin G Winchell
Benjamin Doran
Jennifer P Wang
Aaron G Schmidt
Avrum Spira
Lucrezia Colonna
Michael Farzan
Daniel F Dwyer
Ramnik Xavier
Travis K Hughes
Kerstin Meyer
Christoph Muus
Scott B Snapper
Marc H Wadsworth 2nd
Thu Elizabeth Duong
Manuel Garber
G James Gatter
Shaina L Carroll
Alison Yu
Herbert B Schiller
Joseph Powell
Peter Horvath
Bonnie Berger
Benjamin E Mead
Jeffrey Whitsett
Zhiru Guo
Alexander Misharin
Pascal Barbry
Haeock Lee
Michael von Papen
Sylvie Leroy
Christos Samakovlis
Meshal Ansari
Robert W Finberg
Constantine N Tzouanas
Tushar Desai
Nicholas Banovich
Carly G K Ziegler
Robert Lafyatis
Jennifer M S Sucre
Aviv Regev
JoAnne L Flynn
Emma L Rawlins
Daniel Lingwood
Alexander Tsankov
Martijn Nawijn
Jay Rajagopal
HCA Lung Biological Network
Naftali Kaminski
Ilias Angelidis
Herbert Schiller
Hengqi Betty Zheng
Journal: Cell (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ACE2; COVID-19; ISG; SARS-CoV-2; human

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. 

Retracted: No

PubPeer comments:
 No - the ACE2 receptor is not a gene. ,