SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues
| العنوان: | SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues |
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| المؤلفون: | Alex K. Shalek, Kun Zhang, Christopher W. Peterson, Orit Rosen, Alison Yu, Robert Lafyatis, Samuel W. Kazer, Oliver Eickelberg, Sarah A. Teichmann, Mauricio Rojas, Martijn C. Nawijn, Colin D. Bingle, Thu Elizabeth Duong, Manuel Garber, Magali Plaisant, Philana Ling Lin, Christine S. Falk, Jennifer P. Wang, Xin Sun, Hengqi Betty Zheng, G. James Gatter, Sarah K. Nyquist, Malte Kühnemund, Joachim L. Schultze, Mark A. Krasnow, Maarten van den Berge, Yan Xu, Samuel J. Allon, Daniel F. Dwyer, Peter Horvath, Benjamin Doran, Brian M. Lin, Herbert B. Schiller, Blake M. Hauser, Fabian J. Theis, Avrum Spira, Paul A. Reyfman, Hans-Peter Kiem, Shaina L. Carroll, Zhiru Guo, Douglas P. Shepherd, Michael von Papen, Ian M. Mbano, Michael Farzan, Daniel Lingwood, JoAnne L. Flynn, Christoph Muus, Dana Pe'er, Stephen R. Quake, Travis K. Hughes, Sarah M. Fortune, Sten Linnarson, Chase J. Taylor, Tanya M. Laidlaw, Emma L. Rawlins, Bonnie Berger, Ashraf S. Yousif, Joakim Lundeberg, Jeffrey A. Whitsett, Ian A. Glass, Delphine Gras, Max A. Seibold, Jay Rajagopal, Jared Feldman, Victor Tkachev, Benjamin E. Mead, Joseph E. Powell, Aviv Regev, Alasdair Leslie, Robert W. Finberg, Yuming Cao, Jennifer M.S. Sucre, Marko Vukovic, Scott B. Snapper, Vincent N. Miao, Naftali Kaminski, Laure-Emmanuelle Zaragosi, Caylin G. Winchell, Faith Taliaferro, Marko Nikolic, Ilias Angelidis, Leslie S. Kean, Lucrezia Colonna, Kathleen M. Buchheit, Aaron G. Schmidt, Ramnik J. Xavier, Tushar J. Desai, Marc H. Wadsworth, Joshua A. Boyce, Alexander M. Tsankov, Nora A. Barrett, Pascal Barbry, Muzlifah Haniffa, Heiko Adler, Alvis Brazma, Hannah P. Gideon, Meshal Ansari, Jason R. Spence, Avinash Waghray, Constantine N. Tzouanas, Jose Ordovas-Montanes, Jonathan A. Kropski, Nicholas E. Banovich, Purushothama Rao Tata, Kerstin B. Meyer, Christos Samakovlis, Haeock Lee, Carly G. K. Ziegler, Alexander V. Misharin, Deborah T. Hung, Sylvie Leroy, Julia Bals, Vanessa Mitsialis, Kourosh Saeb-Parsy |
| المساهمون: | Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS), FRM (DEQ20180339158), National Infrastructure France Génomique (Commissariat aux Grands Investissements, ANR-10-INBS-09-03, ANR-10-INBS-09-02), ANR-19-P3IA-0002,3IA@cote d'azur,3IA Côte d'Azur(2019), European Project: 874656,discovAIR, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Koch Institute for Integrative Cancer Research at MIT, Groningen Research Institute for Asthma and COPD (GRIAC) |
| المصدر: | Cell Cell, 2020, 181 (5), pp.1016-1035.e19. ⟨10.1016/j.cell.2020.04.035⟩ Cell, Elsevier, 2020, 181 (5), pp.1016-1035.e19. ⟨10.1016/j.cell.2020.04.035⟩ Cell 181, 1016-1035 (2020) Elsevier Cell, 181(5), 1016-1035.e19. CELL PRESS |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Interferon Type I/immunology, Pneumonia, Viral/virology, Viral/virology, [SDV]Life Sciences [q-bio], ACE2, HIV Infections, non-human primate, HIV Infections/immunology, Mice, 0302 clinical medicine, Single-cell analysis, Alveolar Epithelial Cells/immunology, Interferon, Influenza, Human/immunology, Receptors, Child, Lung, Cells, Cultured, Virus/genetics, 0303 health sciences, Cultured, Serine Endopeptidases, Human/immunology, interferon, Nasal Mucosa/cytology, respiratory system, 3. Good health, Cell biology, Up-Regulation, Interferon Type I, Receptors, Virus, Angiotensin-Converting Enzyme 2, Goblet Cells, Enterocytes/immunology, Single-Cell Analysis, Coronavirus Infections, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Proteases, Coronavirus Infections/virology, Adolescent, Cells, Pneumonia, Viral, Receptors, Virus/genetics, Peptidyl-Dipeptidase A/genetics, Lung injury, Biology, Peptidyl-Dipeptidase A, TMPRSS2, General Biochemistry, Genetics and Molecular Biology, Article, Cell Line, ISG, 03 medical and health sciences, Betacoronavirus, Serine Endopeptidases/metabolism, Downregulation and upregulation, Lung/cytology, Influenza, Human, scRNA-seq, medicine, Ace2, Covid-19, Isg, Sars-cov-2, Human, Influenza, Mouse, Non-human Primate, Scrna-seq, Tuberculosis, Animals, Humans, human, Pandemics, Tuberculosis/immunology, mouse, 030304 developmental biology, Innate immune system, SARS-CoV-2, Betacoronavirus/physiology, Interferon-stimulated gene, COVID-19, Mycobacterium tuberculosis, Pneumonia, Macaca mulatta, respiratory tract diseases, Nasal Mucosa, Enterocytes, Goblet Cells/immunology, Alveolar Epithelial Cells, 030217 neurology & neurosurgery |
| الوصف: | Summary 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. Graphical Abstract Highlights • Meta-analysis of human, non-human primate, and mouse single-cell RNA-seq datasets for putative SARS-CoV-2 targets • Type II pneumocytes, nasal secretory cells, and absorptive enterocytes are ACE2 + TMPRSS2 + • Interferon and influenza increase ACE2 in human nasal epithelia and lung tissue • Mouse Ace2 is not upregulated by interferon, raising implications for disease modeling Analysis of single-cell RNA-seq datasets from human, non-human primate, and mouse barrier tissues identifies putative cellular targets of SARS-CoV-2 on the basis of ACE2 and TMPRSS2 expression. ACE2 represents a previously unappreciated interferon-stimulated gene in human, but not mouse, epithelial tissues, identifying anti-viral induction of a host tissue-protective mechanism, but also a potential means for viral exploitation of the host response. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0092-8674 1097-4172 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::727543612f7db162539d6c42ca832836Test https://doi.org/10.1016/j.cell.2020.04.035Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....727543612f7db162539d6c42ca832836 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00928674 10974172 |
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