scRNA-seq reveals ACE2 and TMPRSS2 expression in TROP2 + Liver Progenitor Cells: Implications in COVID-19 associated Liver Dysfunction

  1. Justine Jia Wen Seow
  2. Rhea Pai
  3. Archita Mishra
  4. Edwin Shepherdson
  5. Tony Kiat Hon Lim
  6. Brian KP Goh
  7. Jerry KY Chan
  8. Pierce KH Chow
  9. Florent Ginhoux
  10. Ramanuj DasGupta
  11. Ankur Sharma

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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 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 TROP2 high progenitors

  • - ACE2 and TMPRSS2 cells express cholangiocyte biased fate markers

  • - ACE2 and TMPRSS2 positive cells are absent in human fetal liver

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      SciScore for 10.1101/2020.03.23.002832: (What is this?)

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      NIH rigor criteria are not applicable to paper type.

      Table 2: Resources

      No key resources detected.

      Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

      Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

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    2. Version published to 10.1101/2020.03.23.002832 on bioRxiv