2019-20 coronavirus outbreak

Cell biology

Molecular biology

Biology

Viral replication

Virology

Receptor

Biochemistry

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Outbreak

Cytopathic effect

Coronavirus disease 2019 (COVID-19)

Immunology

Genetics

Anatomy

Viral entry

Infectious disease (medical specialty)

Internal medicine

Respiratory system

Medicine

Cell

Virus

Disease

Pathogenesis

Pathology

The EMBO Journal

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.

<scp>SARS</scp>‐CoV‐2 receptor<scp>ACE</scp>2 and<scp>TMPRSS</scp>2 are primarily expressed in bronchial transient secretory cells

SARS‐CoV‐2 receptorACE2 andTMPRSS2 are primarily expressed in bronchial transient secretory cells