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

EMBO J. 2020 May 18;39(10):e105114. doi: 10.15252/embj.20105114. Epub 2020 Apr 14.


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.

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

MeSH terms

  • Adult
  • Aging
  • Angiotensin-Converting Enzyme 2
  • Bronchi / cytology*
  • Bronchi / metabolism
  • COVID-19
  • Cells, Cultured
  • Chronic Disease / epidemiology
  • Coronavirus Infections / genetics
  • Epithelial Cells / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression*
  • Germany
  • Goblet Cells / metabolism
  • Humans
  • Lung / cytology*
  • Lung / 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


  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human