多倍体肝细胞状态对肝纤维化、肝硬化以及肿瘤复发的影响OA

Human somatic cells are inherently diploid,and an increase in chromosomal content results in polyploidy.The liver is one of the few human organs that is uniquely enriched in polyploid hepatocytes.Hepatocyte polyploidization participates in liver development and the progression of diverse hepatic diseases.This review systematically integrated recent advances in hepatocyte ploidy research by outlining the principal modes of ploidy transition,delineating distinct ploidy states,and emphasizing the mechanistic differences between binucleated and mononucleated polyploid hepatocytes.We further concentrated on mononucleated polyploid hepatocytes,examining the pathological conditions that underpin their emergence and linking these changes to liver cirrhosis and hepatocellular carcinoma(HCC)recurrence.Across chronic liver diseases that predispose to liver cirrhosis,aberrant expansion of mononucleated polyploid hepatocytes not only accelerated progression liver fibrosis and cirrhosis,but also showed a strong association with clinical outcomes in patients with HCC.Elucidating the regulatory mechanisms that govern mononucleated polyploidization will provide a conceptual foundation for improving the fibrotic and cirrhotic microenvironment and for informing therapeutic strategies aimed at preventing HCC recurrence.