tetano
Editor, Senior Moderator
Cell. 2020 Apr 27. pii: S0092-8674(20)30500-6. doi: 10.1016/j.cell.2020.04.035. [Epub ahead of print]
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 CGK[SUP]1[/SUP], Allon SJ[SUP]2[/SUP], Nyquist SK[SUP]3[/SUP], Mbano IM[SUP]4[/SUP], Miao VN[SUP]5[/SUP], Tzouanas CN[SUP]5[/SUP], Cao Y[SUP]6[/SUP], Yousif AS[SUP]7[/SUP], Bals J[SUP]7[/SUP], Hauser BM[SUP]8[/SUP], Feldman J[SUP]9[/SUP], Muus C[SUP]10[/SUP], Wadsworth MH 2nd[SUP]11[/SUP], Kazer SW[SUP]2[/SUP], Hughes TK[SUP]12[/SUP], Doran B[SUP]13[/SUP], Gatter GJ[SUP]14[/SUP], Vukovic M[SUP]11[/SUP], Taliaferro F[SUP]15[/SUP], Mead BE[SUP]11[/SUP], Guo Z[SUP]6[/SUP], Wang JP[SUP]6[/SUP], Gras D[SUP]16[/SUP], Plaisant M[SUP]17[/SUP], Ansari M[SUP]18[/SUP], Angelidis I[SUP]19[/SUP], Adler H[SUP]20[/SUP], Sucre JMS[SUP]21[/SUP], Taylor CJ[SUP]22[/SUP], Lin B[SUP]23[/SUP], Waghray A[SUP]23[/SUP], Mitsialis V[SUP]24[/SUP], Dwyer DF[SUP]25[/SUP], Buchheit KM[SUP]25[/SUP], Boyce JA[SUP]25[/SUP], Barrett NA[SUP]25[/SUP], Laidlaw TM[SUP]25[/SUP], Carroll SL[SUP]26[/SUP], Colonna L[SUP]27[/SUP], Tkachev V[SUP]28[/SUP], Peterson CW[SUP]29[/SUP], Yu A[SUP]30[/SUP], Zheng HB[SUP]31[/SUP], Gideon HP[SUP]32[/SUP], Winchell CG[SUP]33[/SUP], Lin PL[SUP]34[/SUP], Bingle CD[SUP]35[/SUP], Snapper SB[SUP]24[/SUP], Kropski JA[SUP]36[/SUP], Theis FJ[SUP]37[/SUP], Schiller HB[SUP]19[/SUP], Zaragosi LE[SUP]17[/SUP], Barbry P[SUP]17[/SUP], Leslie A[SUP]38[/SUP], Kiem HP[SUP]29[/SUP], Flynn JL[SUP]32[/SUP], Fortune SM[SUP]39[/SUP], Berger B[SUP]40[/SUP], Finberg RW[SUP]6[/SUP], Kean LS[SUP]28[/SUP], Garber M[SUP]6[/SUP], Schmidt AG[SUP]8[/SUP], Lingwood D[SUP]7[/SUP], Shalek AK[SUP]41[/SUP], Ordovas-Montanes J[SUP]42[/SUP]; HCA Lung Biological Network. Electronic address: [email]lung-network@humancellatlas.org[/email]; HCA Lung Biological Network.
Collaborators (56)
Author information
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.
Copyright ? 2020 The Authors. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
ACE2; COVID-19; ISG; SARS-CoV-2; human; influenza; interferon; mouse; non-human primate; scRNA-seq
PMID:32413319DOI:10.1016/j.cell.2020.04.035
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 CGK[SUP]1[/SUP], Allon SJ[SUP]2[/SUP], Nyquist SK[SUP]3[/SUP], Mbano IM[SUP]4[/SUP], Miao VN[SUP]5[/SUP], Tzouanas CN[SUP]5[/SUP], Cao Y[SUP]6[/SUP], Yousif AS[SUP]7[/SUP], Bals J[SUP]7[/SUP], Hauser BM[SUP]8[/SUP], Feldman J[SUP]9[/SUP], Muus C[SUP]10[/SUP], Wadsworth MH 2nd[SUP]11[/SUP], Kazer SW[SUP]2[/SUP], Hughes TK[SUP]12[/SUP], Doran B[SUP]13[/SUP], Gatter GJ[SUP]14[/SUP], Vukovic M[SUP]11[/SUP], Taliaferro F[SUP]15[/SUP], Mead BE[SUP]11[/SUP], Guo Z[SUP]6[/SUP], Wang JP[SUP]6[/SUP], Gras D[SUP]16[/SUP], Plaisant M[SUP]17[/SUP], Ansari M[SUP]18[/SUP], Angelidis I[SUP]19[/SUP], Adler H[SUP]20[/SUP], Sucre JMS[SUP]21[/SUP], Taylor CJ[SUP]22[/SUP], Lin B[SUP]23[/SUP], Waghray A[SUP]23[/SUP], Mitsialis V[SUP]24[/SUP], Dwyer DF[SUP]25[/SUP], Buchheit KM[SUP]25[/SUP], Boyce JA[SUP]25[/SUP], Barrett NA[SUP]25[/SUP], Laidlaw TM[SUP]25[/SUP], Carroll SL[SUP]26[/SUP], Colonna L[SUP]27[/SUP], Tkachev V[SUP]28[/SUP], Peterson CW[SUP]29[/SUP], Yu A[SUP]30[/SUP], Zheng HB[SUP]31[/SUP], Gideon HP[SUP]32[/SUP], Winchell CG[SUP]33[/SUP], Lin PL[SUP]34[/SUP], Bingle CD[SUP]35[/SUP], Snapper SB[SUP]24[/SUP], Kropski JA[SUP]36[/SUP], Theis FJ[SUP]37[/SUP], Schiller HB[SUP]19[/SUP], Zaragosi LE[SUP]17[/SUP], Barbry P[SUP]17[/SUP], Leslie A[SUP]38[/SUP], Kiem HP[SUP]29[/SUP], Flynn JL[SUP]32[/SUP], Fortune SM[SUP]39[/SUP], Berger B[SUP]40[/SUP], Finberg RW[SUP]6[/SUP], Kean LS[SUP]28[/SUP], Garber M[SUP]6[/SUP], Schmidt AG[SUP]8[/SUP], Lingwood D[SUP]7[/SUP], Shalek AK[SUP]41[/SUP], Ordovas-Montanes J[SUP]42[/SUP]; HCA Lung Biological Network. Electronic address: [email]lung-network@humancellatlas.org[/email]; HCA Lung Biological Network.
Collaborators (56)
Author information
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.
Copyright ? 2020 The Authors. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
ACE2; COVID-19; ISG; SARS-CoV-2; human; influenza; interferon; mouse; non-human primate; scRNA-seq
PMID:32413319DOI:10.1016/j.cell.2020.04.035