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SARS-CoV-2 Receptor ACE2 is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Enriched in Specific Cell Subsets Across Tissues

42 Pages Posted: 17 Mar 2020 Sneak Peek Status: Published

See all articles by Carly Ziegler

Carly Ziegler

Harvard University - Ragon Institute of MGH, MIT and Harvard

Samuel J. Allon

Massachusetts Institute of Technology (MIT) - Institute for Medical Engineering and Science

Sarah K. Nyquist

Harvard University - Ragon Institute of MGH, MIT and Harvard

Ian Mbano

Africa Health Research Institute

Vincent N. Miao

Harvard University - Ragon Institute of MGH, MIT and Harvard

Yuming Cao

University of Massachusetts Boston

Ashraf S. Yousif

Harvard University - Ragon Institute of MGH, MIT and Harvard

Julia Bals

Ragon Institute of MGH, MIT and Harvard

Blake M. Hauser

Harvard University - Ragon Institute of MGH, MIT and Harvard

Jared Feldman

Masssachusetts Institute of Technology and Harvard University - Ragon Institute

Christoph Muus

Masssachusetts Institute of Technology and Harvard University - Broad Institute

Marc H. Wadsworth II

Masssachusetts Institute of Technology and Harvard University - Broad Institute

Samuel Kazer

Massachusetts Institute of Technology (MIT) - David H. Koch Institute for Integrative Cancer Research

Travis K. Hughes

Harvard University - Ragon Institute of MGH, MIT and Harvard

Benjamin Doran

Boston Children’s Hospital

G. James Gatter

Massachusetts Institute of Technology (MIT) - Institute for Medical Engineering and Science

Marko Vukovic

Masssachusetts Institute of Technology and Harvard University - Broad Institute

Constantine N. Tzouanas

Harvard University - Ragon Institute of MGH, MIT and Harvard

Faith Taliaferro

Masssachusetts Institute of Technology and Harvard University - Broad Institute

Zhiru Guo

University of Massachusetts Worcester - Medical School

Jennifer P. Wang

University of Massachusetts Worcester - Medical School

Daniel F. Dwyer

Brigham and Women’s Hospital

Kathleen M. Buchheit

Brigham and Women’s Hospital

Joshua Boyce

Brigham and Women’s Hospital

Nora A. Barrett

Brigham and Women's Hospital

Tanya M. Laidlaw

Harvard University - Brigham and Women's Hospital

Shaina L. Carroll

University of California, Berkeley

Lucrezia Colonna

University of Washington

Victor Tkachev

Boston Children's Hospital

Alison Yu

Boston Children's Hospital

Henqi Betty Zheng

Seattle Children's Hospital

Hannah P. Gideon

University of Pittsburgh - Department of Microbiology and Molecular Genetics

Caylin G. Winchell

University of Pittsburgh

Philana L. Lin

University of Pittsburgh - Department of Pediatrics

Bonnie Berger

Massachusetts Institute of Technology (MIT)

Alasdair Leslie

Africa Health Research Institute

JoAnne L. Flynn

University of Pittsburgh - Department of Microbiology and Molecular Genetics

Sarah M. Fortune

Harvard University - Ragon Institute of MGH, MIT and Harvard

Robert W. Finberg

University of Massachusetts Boston

Leslie Kean

Dana-Farber Cancer Institute - Boston Children’s Hospital

Manuel Garber

University of Massachusetts Boston

Aaron Schmidt

Harvard University - Ragon Institute of MGH, MIT and Harvard

Daniel Lingwood

Harvard University - Ragon Institute of MGH, MIT and Harvard

Alex K. Shalek

Masssachusetts Institute of Technology and Harvard University - Broad Institute

Jose Ordovas-Montanes

Masssachusetts Institute of Technology and Harvard University - Broad Institute

HCA Lung Biological Network

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Abstract

There is pressing urgency to better understand the pathogenesis of the severe acute respiratory syndrome (SARS) coronavirus (CoV) clade SARS-CoV-2. SARS-CoV-2, like SARS-CoV, utilizes ACE2 to bind host cells. While initial SARS-CoV-2 cell entry and infection depend on ACE2 in concert with the protease TMPRSS2 for spike (S) protein activation, the specific cell subsets targeted by SARS-CoV-2 in host tissues, and the factors that regulate ACE2 expression, remain unknown. Here, we leverage human and non-human primate (NHP) single-cell RNA-sequencing (scRNA-seq) datasets to uncover the cell subsets that may serve as cellular targets of SARS-CoV-2. We identify ACE2/TMPRSS2 co-expressing cells within type II pneumocytes, absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discover that ACE2 is an interferon-stimulated gene (ISG) in human barrier tissue epithelial cells. Thus, SARS-CoV-2 may exploit IFN-driven upregulation of ACE2, a key tissue-protective mediator during lung injury, to enhance infection.

Keywords: SARS-CoV-2, single-cell RNA-sequencing, ACE2, interferon, interferon stimulated gene, barrier tissues, human, non-human primate, epithelial tissues, host-pathogen

Suggested Citation

Ziegler, Carly and Allon, Samuel J. and Nyquist, Sarah K. and Mbano, Ian and Miao, Vincent N. and Cao, Yuming and Yousif, Ashraf S. and Bals, Julia and Hauser, Blake M. and Feldman, Jared and Muus, Christoph and Wadsworth II, Marc H. and Kazer, Samuel and Hughes, Travis K. and Doran, Benjamin and Gatter, G. James and Vukovic, Marko and Tzouanas, Constantine N. and Taliaferro, Faith and Guo, Zhiru and Wang, Jennifer P. and Dwyer, Daniel F. and Buchheit, Kathleen M. and Boyce, Joshua and Barrett, Nora A. and Laidlaw, Tanya M. and Carroll, Shaina L. and Colonna, Lucrezia and Tkachev, Victor and Yu, Alison and Zheng, Henqi Betty and Gideon, Hannah P. and Winchell, Caylin G. and Lin, Philana L. and Berger, Bonnie and Leslie, Alasdair and Flynn, JoAnne L. and Fortune, Sarah M. and Finberg, Robert W. and Kean, Leslie and Garber, Manuel and Schmidt, Aaron and Lingwood, Daniel and Shalek, Alex K. and Ordovas-Montanes, Jose and Lung Biological Network, HCA, SARS-CoV-2 Receptor ACE2 is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Enriched in Specific Cell Subsets Across Tissues. Available at SSRN: https://ssrn.com/abstract=3555145 or http://dx.doi.org/10.2139/ssrn.3555145
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Carly Ziegler

Harvard University - Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Samuel J. Allon

Massachusetts Institute of Technology (MIT) - Institute for Medical Engineering and Science ( email )

Cambridge, MA
United States

Sarah K. Nyquist

Harvard University - Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Ian Mbano

Africa Health Research Institute ( email )

719 Umbilo Road
K-RITH Tower Building, level 3
Durban, KwaZulu-Natal 4001
South Africa

Vincent N. Miao

Harvard University - Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Yuming Cao

University of Massachusetts Boston

100 William T Morrissey Blvd
Boston, MA 02125
United States

Ashraf S. Yousif

Harvard University - Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Julia Bals

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Blake M. Hauser

Harvard University - Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Jared Feldman

Masssachusetts Institute of Technology and Harvard University - Ragon Institute ( email )

Boston, MA
United States

Christoph Muus

Masssachusetts Institute of Technology and Harvard University - Broad Institute ( email )

415 Main Street
Cambridge, MA 02142
United States

Marc H. Wadsworth II

Masssachusetts Institute of Technology and Harvard University - Broad Institute ( email )

415 Main Street
Cambridge, MA 02142
United States

Samuel Kazer

Massachusetts Institute of Technology (MIT) - David H. Koch Institute for Integrative Cancer Research

77 Massachusetts Avenue
50 Memorial Drive
Cambridge, MA 02139-4307
United States

Travis K. Hughes

Harvard University - Ragon Institute of MGH, MIT and Harvard

Boston, MA
United States

Benjamin Doran

Boston Children’s Hospital

300 Longwood Avenue
Boston, MA 02115
United States

G. James Gatter

Massachusetts Institute of Technology (MIT) - Institute for Medical Engineering and Science ( email )

Cambridge, MA
United States

Marko Vukovic

Masssachusetts Institute of Technology and Harvard University - Broad Institute

415 Main Street
Cambridge, MA 02142
United States

Constantine N. Tzouanas

Harvard University - Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Faith Taliaferro

Masssachusetts Institute of Technology and Harvard University - Broad Institute ( email )

415 Main Street
Cambridge, MA 02142
United States

Zhiru Guo

University of Massachusetts Worcester - Medical School ( email )

55 Lake Avenue North
Worcester, MA 01655
United States

Jennifer P. Wang

University of Massachusetts Worcester - Medical School

55 Lake Avenue North
Worcester, MA 01655
United States

Daniel F. Dwyer

Brigham and Women’s Hospital

75 Francis St.
Boston, MA 02115
United States

Kathleen M. Buchheit

Brigham and Women’s Hospital ( email )

75 Francis St.
Boston, MA 02115
United States

Joshua Boyce

Brigham and Women’s Hospital

Nora A. Barrett

Brigham and Women's Hospital ( email )

75 Francis St.
Boston, MA 02115
United States

Tanya M. Laidlaw

Harvard University - Brigham and Women's Hospital ( email )

75 Francis St.
Boston, MA 02115
United States

Shaina L. Carroll

University of California, Berkeley

310 Barrows Hall
Berkeley, CA 94720
United States

Lucrezia Colonna

University of Washington

Seattle, WA 98195
United States

Victor Tkachev

Boston Children's Hospital ( email )

401 Park Drive
Landmark 5th Floor East
Boston, MA 02115
United States

Alison Yu

Boston Children's Hospital

401 Park Drive
Landmark 5th Floor East
Boston, MA 02115
United States

Henqi Betty Zheng

Seattle Children's Hospital ( email )

4800 Sand Point Way NE
Seattle, WA 98105
United States

Hannah P. Gideon

University of Pittsburgh - Department of Microbiology and Molecular Genetics ( email )

450 Technology Drive
Pittsburgh, PA 15219
United States

Caylin G. Winchell

University of Pittsburgh ( email )

135 N Bellefield Ave
Pittsburgh, PA 15260
United States

Philana L. Lin

University of Pittsburgh - Department of Pediatrics ( email )

Pittsburgh, PA
United States

Bonnie Berger

Massachusetts Institute of Technology (MIT) ( email )

77 Massachusetts Avenue
50 Memorial Drive
Cambridge, MA 02139-4307
United States

Alasdair Leslie

Africa Health Research Institute

719 Umbilo Road
K-RITH Tower Building, level 3
Durban, KwaZulu-Natal 4001
South Africa

JoAnne L. Flynn

University of Pittsburgh - Department of Microbiology and Molecular Genetics ( email )

450 Technology Drive
Pittsburgh, PA 15219
United States

Sarah M. Fortune

Harvard University - Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Robert W. Finberg

University of Massachusetts Boston ( email )

100 William T Morrissey Blvd
Boston, MA 02125
United States

Leslie Kean

Dana-Farber Cancer Institute - Boston Children’s Hospital ( email )

300 Longwood Avenue
Boston, MA 02115
United States

Manuel Garber

University of Massachusetts Boston ( email )

100 William T Morrissey Blvd
Boston, MA 02125
United States

Aaron Schmidt

Harvard University - Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Daniel Lingwood

Harvard University - Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Alex K. Shalek

Masssachusetts Institute of Technology and Harvard University - Broad Institute ( email )

415 Main Street
Cambridge, MA 02142
United States

Jose Ordovas-Montanes (Contact Author)

Masssachusetts Institute of Technology and Harvard University - Broad Institute ( email )

415 Main Street
Cambridge, MA 02142
United States

No contact information is available for HCA Lung Biological Network

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