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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.

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Dataset ID Description Technology Samples
EGAD00001006185 Illumina HiSeq 4000 16
Publications Citations
SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells.
EMBO J 39: 2020 e105114
688
Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers.
Cell Rep Med 2: 2021 100421
15
SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis.
Cell 184: 2021 6243-6261.e27
208
Identification of Transcription Factors Regulating SARS-CoV-2 Tropism Factor Expression by Inferring Cell-Type-Specific Transcriptional Regulatory Networks in Human Lungs.
Viruses 14: 2022 837
1
ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19.
Nat Commun 13: 2022 4484
10