SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells.

Autor: Lukassen S; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.; Center for Digital Health, Berlin Institute of Health (BIH), Berlin, Germany., Chua RL; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.; Center for Digital Health, Berlin Institute of Health (BIH), Berlin, Germany., Trefzer T; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.; Center for Digital Health, Berlin Institute of Health (BIH), Berlin, Germany., Kahn NC; Department of Pneumology and Respiratory Critical Care Medicine, Center for interstitial and rare lung diseases, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany.; Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany., Schneider MA; Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.; Translational Research Unit, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany., Muley T; Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.; Translational Research Unit, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany., Winter H; Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.; Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany., Meister M; Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.; Translational Research Unit, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany., Veith C; Division of Redox Regulation, German Cancer Research Center (DKFZ) , Heidelberg, Germany., Boots AW; Faculty of Health, Medicine and Life Sciences, Department of Pharmacology and Toxicology, NUTRIM School of Nutrition, Translational Research and Metabolism, Maastricht University, Maastricht, the Netherlands., Hennig BP; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.; Center for Digital Health, Berlin Institute of Health (BIH), Berlin, Germany., Kreuter M; Department of Pneumology and Respiratory Critical Care Medicine, Center for interstitial and rare lung diseases, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany., Conrad C; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany., Eils R; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.; Center for Digital Health, Berlin Institute of Health (BIH), Berlin, Germany.; Health Data Science Unit, Heidelberg University Hospital and BioQuant, Heidelberg, Germany.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2020 May 18; Vol. 39 (10), pp. e105114. Date of Electronic Publication: 2020 Apr 14.
DOI: 10.15252/embj.20105114
Abstrakt: The SARS-CoV-2 pandemic affecting the human respiratory system severely challenges public health and urgently demands for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and replication. SARS-CoV-2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. While TMPRSS2 is strongly expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type. Interestingly, these transiently differentiating cells show an enrichment for pathways related to RHO GTPase function and viral processes suggesting increased vulnerability for SARS-CoV-2 infection. Our data provide a rich resource for future investigations of COVID-19 infection and pathogenesis.
(© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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