Authors: Seow, Justine Jia Wen; Pai, Rhea; Mishra, Archita; Shepherdson, Edwin; Lim, Tony Kiat Hon; Goh, Brian K. P.; Chan, Jerry K. Y.; Chow, Pierce K. H.; Ginhoux, Florent; DasGupta, Ramanuj; Sharma, Ankur
Online: https://www.frontiersin.org/articles/10.3389/fmed.2021.603374/full
Issue: Front Med (Lausanne). 2021 Apr 22;8:603374.
Abstract
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 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 analysed ~300,000 single cells across five different (i.e. human fetal, healthy, cirrhotic, tumor and adjacent normal) liver tissues types. We report the co-expression of ACE2 and TMPRSS2 in a TROP2+ liver progenitor population. Importantly, we detected enrichment of this cell population in cirrhotic liver when compared to tumor tissue. These results indicated that in COVID-19 associated liver dysfunction and cell death, viral infection of TROP2+ progenitors in liver may significantly impaired the liver regeneration in patients with liver cirrhosis.
