Sequencing almost 60,000 cells, researchers have found that certain cilia progenitor cells have gene transcripts for ACE2 and co-factor TMPRSS2, enabling COVID-19 infection.
The researchers are from the Berlin Institute of Health (BIH), Charité – Universitätsmedizin Berlin and the Thorax Clinic at Heidelberg University Hospital, whose collaboration is taking place under the auspices of the German Center for Lung Research (DZL).
“We analysed a total of nearly 60,000 cells to determine whether they activated the gene for the receptor and potential co-factors, thus in principle allowing them to be infected by the coronavirus,” said Soeren Lukassen, one of the lead authors of the study. “We only found the gene transcripts for ACE2 and for the co-factor TMPRSS2 in very few cells and only in very small numbers.”
According to the researchers, they discovered that the receptor for COVID-19 is expressed in certain progenitor cells. These cells normally develop into respiratory tract cells lined with hair-like projections called cilia that sweep mucus and bacteria out of the lungs.
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 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.
Reference & Source Information: https://www.drugtargetreview.com/, https://www.embopress.org/
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