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

Frontiers in Medicine

Brian K. P. Goh¹  Tony Kiat Hon Lim²  Edwin Shepherdson³  Jerry K. Y. Chan³  Pierce K. H. Chow⁴  Ramanuj DasGupta⁵  Rhea Pai⁵  Justine Jia Wen Seow⁵  Ankur Sharma⁶  Archita Mishra⁷  Florent Ginhoux⁸ 

[1] Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore;Department of Pathology, Singapore General Hospital, Singapore, Singapore;Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore, Singapore;Division of Surgical Oncology, National Cancer Centre, Singapore, Singapore;Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore;Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore;Harry Perkins Institute of Medical Research, Queen Elizabeth II Medical Centre and Centre for Medical Research, Nedlands, WA, Australia;Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia;Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore;Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore;Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, China;Translational Immunology Institute, SingHealth Duke-National University of Singapore Academic Medical Centre, Singapore, Singapore;

关键词: SARS-CoV-2;    COVID-19;    ACE2;    tmprss2;    Trop2;    liver;    ScRNA-seq;   

DOI  :  10.3389/fmed.2021.603374

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY