Perivenous Stellate Cells Are the Main Source of Myofibroblasts and Cancer‐Associated Fibroblasts Formed After Chronic Liver Injuries. Issue 3 (15th September 2021)

• Record Type: Journal Article
• Authors: Wang, Shan‐Shan; Tang, Xinyu Thomas; Lin, Minghui; Yuan, Jia; Peng, Yi Jacky; Yin, Xiujuan; Shang, GuoGuo; Ge, Gaoxiang; Ren, Zhenggang; Zhou, Bo O.
• Is Part Of: Hepatology. Volume 74:Issue 3(2021)
• Page Start: 1578
• Page End: 1594
• Publication Date: 2021-09-15
• Subjects: Heart -- Diseases -- Nursing -- Periodicals; Lungs -- Diseases -- Nursing -- Periodicals; Intensive care nursing -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1002/hep.31848
• Languages: English
• ISSNs: 0270-9139

Abstract

Abstract : Background and Aims: Studies of the identity and pathophysiology of fibrogenic HSCs have been hampered by a lack of genetic tools that permit specific and inducible fate‐mapping of these cells in vivo . Here, by single‐cell RNA sequencing of nonparenchymal cells from mouse liver, we identified transcription factor 21 ( Tcf21 ) as a unique marker that restricted its expression to quiescent HSCs. Approach and Results: Tracing Tcf21 + cells by Tcf21 ‐CreER (Cre‐Estrogen Receptor fusion protein under the control of Tcf21 gene promoter) targeted ~10% of all HSCs, most of which were located at periportal and pericentral zones. These HSCs were quiescent under steady state but became activated on injuries, generating 62%‐67% of all myofibroblasts in fibrotic livers and ~85% of all cancer‐associated fibroblasts (CAFs) in liver tumors. Conditional deletion of Transforming Growth Factor Beta Receptor 2 ( Tgfbr2 ) by Tcf21 ‐CreER blocked HSC activation, compromised liver fibrosis, and inhibited liver tumor progression. Conclusions: In conclusion, Tcf21 ‐CreER–targeted perivenous stellate cells are the main source of myofibroblasts and CAFs in chronically injured livers. TGF‐β signaling links HSC activation to liver fibrosis and tumorigenesis.