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

Soeren Lukassen, Robert Lorenz Chua, Timo Trefzer, Nicolas C. Kahn, Marc A. Schneider, Thomas Muley, Hauke Winter, Michael Meister, Carmen Veith, Agnes W. Boots, Bianca P. Hennig, Michael Kreuter*, Christian Conrad*, Roland Eils*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article number105114
Number of pages15
JournalThe Embo Journal
Volume39
Issue number10
Early online date1 Jan 2020
DOIs
Publication statusPublished - 18 May 2020

Keywords

  • COVID-19
  • epithelial differentiation
  • FURIN
  • Human Cell Atlas
  • respiratory tract
  • RESPIRATORY SYNDROME CORONAVIRUS
  • SARS-CORONAVIRUS
  • EPITHELIAL-CELLS
  • FUNCTIONAL RECEPTOR
  • SPIKE
  • ENTRY
  • PATHOGENESIS
  • ACTIVATION
  • PNEUMONIA
  • 2019-NCOV

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