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scRNA-seq reveals ACE2 and TMPRSS2 expression in TROP2+ Liver Progenitor Cells: Implications in COVID-19 associated Liver Dysfunction
Justine Jia Wen Seow.
Rhea Pai.
Archita Mishra.
Edwin Shepherdson.
Tony Kiat Hon Lim.
Brian K P Goh.
Jerry KY Chan.
Pierce KH Chow.
Florent Ginhoux.
Ramanuj DasGupta.
Ankur Sharma.
Acceso Abierto
Atribución-NoComercial-SinDerivadas
10.1101/2020.03.23.002832
The recent pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 was first reported in China (December 2019) and now prevalent in [~]170 countries across the globe. Entry of SARS-CoV-2 into mammalian cells require the binding of viral Spike (S) proteins to the ACE2 (angiotensin converting enzyme 2) receptor. Once entered the S protein is primed by a specialised serine protease, TMPRSS2 (Transmembrane Serine Protease 2) in the host cell. Importantly, beside respiratory symptoms, consistent with other common respiratory virus infection when patients become viraemic, a significant number of COVID-19 patients also develop liver comorbidities. We explored if 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 employed single-cell RNA-seq (scRNA-seq) to survey the human liver and identified potentially implicated liver cell-type for viral ingress. We report the co-expression of ACE2 and TMPRSS2 in a TROP2+ liver progenitor population. Importantly, we fail to detect the expression of ACE2 in hepatocyte or any other liver (immune and stromal) cell types. These results indicated that in COVID-19 associated liver dysfunction and cell death, viral infection of TROP2+ progenitors in liver may significantly impaired liver regeneration and could lead to pathology. Highlights- EPCAM+ Liver progenitors co-express ACE2 and TMPRSS2 - ACE2 and TMPRSS2 expression is highest in TROP2high progenitors - ACE2 and TMPRSS2 cells express cholangiocyte biased fate markers - ACE2 and TMPRSS2 positive cells are absent in human fetal liver
www.biorxiv.org
2020
Artículo
https://www.biorxiv.org/content/10.1101/2020.03.23.002832v1.full.pdf
Inglés
VIRUS RESPIRATORIOS
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