Derepression of the epithelial transcription factor GRHL2 promotes direct hepatocyte-to-cholangiocyte transdifferentiation.

ABSTRACT: The liver's regenerative capacity is underscored by the plasticity potential of adult hepatocytes. In this context, hepatocyte-to-cholangiocyte transdifferentiation (HCT) has been ascribed with pro-regenerative functions in animal models and is a feature of end-stage human chronic liver diseases. While dampened activities of hepatocyte identity transcription factors (TFs) underlay HCT, how the cholangiocyte transcriptional program is implemented is poorly defined. Here, we identify that HCT does not involve transitioning through a hepatoblast-like transcriptional program. Furthermore, we show that HCT primarily involves induction of the archetypal transcriptional program of monopolarized epithelial cells initially repressed in hepatocytes. Indeed, HCT requires relieving H3K27me3-mediated a

SUBMITTER: Vasseur L 

PROVIDER: S-EPMC12714216 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature