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

Publisher: Wiley Blackwell Country of Publication: England NLM ID: 8208664 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2075 (Electronic) Linking ISSN: 02614189 NLM ISO Abbreviation: EMBO J Subsets: MEDLINE

Publication: 2014- : London : Wiley Blackwell
Original Publication: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982-

Gene Expression* ; Single-Cell Analysis*; Bronchi/*cytology ; Lung/*cytology ; Peptidyl-Dipeptidase A/*genetics ; Serine Endopeptidases/*genetics; Adult ; Aging ; Angiotensin-Converting Enzyme 2 ; Bronchi/metabolism ; COVID-19 ; Cells, Cultured ; Chronic Disease/epidemiology ; Coronavirus Infections/genetics ; Epithelial Cells/metabolism ; Female ; Gene Expression Profiling ; Germany ; Goblet Cells/metabolism ; Humans ; Lung/metabolism ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral/genetics ; Reference Standards ; Sequence Analysis, RNA ; Sex Characteristics ; Smoking ; Tissue Banks

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.)

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874710 International EC|Horizon 2020 Framework Programme (H2020); 82DZL00402 International German Center for Lung Research (DLZ); International European Respiratory Society (STRTF - 201804-00377) - fellowship CV

Keywords: FURIN; COVID-19; Human Cell Atlas; epithelial differentiation; respiratory tract

EC 3.4.15.1 (Peptidyl-Dipeptidase A)
EC 3.4.17.23 (ACE2 protein, human)
EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
EC 3.4.21.- (Serine Endopeptidases)
EC 3.4.21.- (TMPRSS2 protein, human)

Date Created: 20200405 Date Completed: 20200520 Latest Revision: 20231111

20231111

PMC7232010

10.15252/embj.20105114

32246845