State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
FEBS J. 2023 Dec;290(24):5674-5688. doi: 10.1111/febs.16930. Epub 2023 Aug 23.
The liver is one of the few organs that retain the capability to regenerate in adult mammals. This regeneration process is mainly facilitated by the dynamic behavior of hepatocytes, which are the major functional constituents in the liver. In response to liver injury, hepatocytes undergo remarkable alterations, such as reprogramming, wherein they lose their original identity and acquire properties from other cells. This phenomenon of hepatocyte reprogramming, coupled with hepatocyte expansion, plays a central role in liver regeneration, and its underlying mechanisms are complex and multifaceted. Understanding the fate of reprogrammed hepatocytes and the mechanisms of their conversion has significant implications for the development of innovative therapeutics for liver diseases. Herein, we review the plasticity of hepatocytes in response to various forms of liver injury, with a focus on injury-induced hepatocyte reprogramming. We provide a comprehensive summary of current knowledge on the molecular and cellular mechanisms governing hepatocyte reprogramming, specifically in the context of liver regeneration, providing insight into potential applications of this process in the treatment of liver disorders, including chronic liver diseases and liver cancer.
肝脏是少数几种在成年哺乳动物中具有再生能力的器官之一。这种再生过程主要是由肝细胞的动态行为所促进的,肝细胞是肝脏的主要功能成分。在肝损伤的情况下,肝细胞经历显著的改变,例如重编程,在此过程中它们失去了原有的身份,并获得来自其他细胞的特性。这种肝细胞重编程的现象,加上肝细胞的扩增,在肝脏再生中起着核心作用,其潜在的机制是复杂和多方面的。了解重编程肝细胞的命运及其转化的机制对于开发肝脏疾病的创新疗法具有重要意义。在此,我们综述了肝细胞对各种形式的肝损伤的可塑性反应,重点关注损伤诱导的肝细胞重编程。我们全面总结了目前关于调控肝细胞重编程的分子和细胞机制的知识,特别是在肝脏再生的背景下,为该过程在治疗肝脏疾病,包括慢性肝脏疾病和肝癌中的潜在应用提供了深入了解。