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Single-Cell RNA-seq Reveals Angiotensin-Converting Enzyme 2 and Transmembrane Serine Protease 2 Expression in TROP2+ Liver Progenitor Cells: Implications in Coronavirus Disease 2019-Associated Liver Dysfunction
- Source :
- Frontiers in Medicine, Vol 8 (2021)
- Publication Year :
- 2021
- Publisher :
- Frontiers Media S.A., 2021.
-
Abstract
- The recent coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2. COVID-19 was first reported in China (December 2019) and is now prevalent across the globe. Entry of severe acute respiratory syndrome coronavirus 2 into mammalian cells requires the binding of viral Spike (S) proteins to the angiotensin-converting enzyme 2 receptor. Once entered, the S protein is primed by a specialized serine protease, transmembrane serine protease 2 in the host cell. Importantly, besides the respiratory symptoms that are consistent with other common respiratory virus infections when patients become viremic, a significant number of COVID-19 patients also develop liver comorbidities. We explored whether a specific target cell-type in the mammalian liver could be implicated in disease pathophysiology other than the general deleterious response to cytokine storms. Here, we used single-cell RNA-seq to survey the human liver and identified potentially implicated liver cell-type for viral ingress. We analyzed ~300,000 single cells across five different (i.e., human fetal, healthy, cirrhotic, tumor, and adjacent normal) liver tissue types. This study reports on the co-expression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 in a TROP2+ liver progenitor population. Importantly, we detected enrichment of this cell population in the cirrhotic liver when compared with tumor tissue. These results indicated that in COVID-19-associated liver dysfunction and cell death, a viral infection of TROP2+ progenitors in the liver might significantly impair liver regeneration in patients with liver cirrhosis.
- Subjects :
- SARS-CoV-2
COVID-19
ACE2
tmprss2
Trop2
liver
Medicine (General)
R5-920
Subjects
Details
- Language :
- English
- ISSN :
- 2296858X
- Volume :
- 8
- Database :
- Directory of Open Access Journals
- Journal :
- Frontiers in Medicine
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.73e8e57f0fe643f5a695f50aaee9ed88
- Document Type :
- article
- Full Text :
- https://doi.org/10.3389/fmed.2021.603374