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Article ; Online: Single-Cell RNA-seq Reveals Angiotensin-Converting Enzyme 2 and Transmembrane Serine Protease 2 Expression in TROP2+ Liver Progenitor Cells

Justine Jia Wen Seow / Rhea Pai / Archita Mishra / Edwin Shepherdson / Tony Kiat Hon Lim / Brian K. P. Goh / Jerry K. Y. Chan / Pierce K. H. Chow / Florent Ginhoux / Ramanuj DasGupta / Ankur Sharma

Frontiers in Medicine, Vol

Implications in Coronavirus Disease 2019-Associated Liver Dysfunction

2021  Volume 8

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 ... ...

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.
Keywords SARS-CoV-2 ; COVID-19 ; ACE2 ; tmprss2 ; Trop2 ; liver ; Medicine (General) ; R5-920
Subject code 610
Language English
Publishing date 2021-04-01T00:00:00Z
Publisher Frontiers Media S.A.
Document type Article ; Online
Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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