Science and Research

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

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.

  • Lukassen, S.
  • Chua, R. L.
  • Trefzer, T.
  • Kahn, N. C.
  • Schneider, M. A.
  • Muley, T.
  • Winter, H.
  • Meister, M.
  • Veith, C.
  • Boots, A. W.
  • Hennig, B. P.
  • Kreuter, M.
  • Conrad, C.
  • Eils, R.

Keywords

  • Adult
  • Aging
  • Bronchi/*cytology/metabolism
  • Cells, Cultured
  • Chronic Disease/epidemiology
  • Coronavirus Infections/genetics
  • Epithelial Cells/metabolism
  • Female
  • *Gene Expression
  • Gene Expression Profiling
  • Germany
  • Goblet Cells/metabolism
  • Humans
  • Lung/*cytology/metabolism
  • Male
  • Middle Aged
  • Pandemics
  • Peptidyl-Dipeptidase A/*genetics
  • Pneumonia, Viral/genetics
  • Reference Standards
  • Sequence Analysis, RNA
  • Serine Endopeptidases/*genetics
  • Sex Characteristics
  • *Single-Cell Analysis
  • Smoking
  • Tissue Banks
  • * furin
  • *covid-19
  • *Human Cell Atlas
  • *epithelial differentiation
  • *respiratory tract
Publication details
DOI: 10.15252/embj.20105114
Journal: EMBO J
Pages: e105114 
Number: 10
Work Type: Original
Location: Assoziierter Partner, TLRC
Disease Area: PALI
Partner / Member: BIH, Thorax
Access-Number: 32246845
See publication on PubMed

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