The stable repression of mesenchymal program is required for hepatocyte identity: a novel role for hepatocyte nuclear factor 4α.
type: Dataset
description: UNLABELLED: The concept that cellular terminal differentiation is stably maintained once development is complete has been questioned by numerous observations showing that differentiated epithelium may undergo an epithelial-to-mesenchymal transition (EMT) program. EMT and the reverse process, mesenchymal-to-epithelial transition (MET), are typical events of development, tissue repair, and tumor progression. In this study, we aimed to clarify the molecular mechanisms underlying these phenotypic conversions in hepatocytes. Hepatocyte nuclear factor 4α (HNF4α) was overexpressed in different hepatocyte cell lines and the resulting gene expression profile was determined by real-time quantitative polymerase chain reaction. HNF4α recruitment on promoters of both mesenchymal and EMT regulator genes was determined by way of electrophoretic mobility shift assay and chromatin immunoprecipitation. The effect of HNF4α depletion was assessed in silenced cells and in the context of the whole liver of HNF4 knockout animals. Our results identified key EMT regulators and mesenchymal genes as new targets of HNF4α. HNF4α, in cooperation with its target HNF1α, directly inhibits transcription of the EMT master regulatory genes Snail, Slug, and HMGA2 and of several mesenchymal markers. HNF4α-mediated repression of EMT genes induces MET in hepatomas, and its silencing triggers the mesenchymal program in differentiated hepatocytes both in cell culture and in the whole liver. CONCLUSION: The pivotal role of HNF4α in the induction and maintenance of hepatocyte differentiation should also be ascribed to its capacity to continuously repress the mesenchymal program; thus, both HNF4α activator and repressor functions are necessary for the identity of hepatocytes.
landing page: 0270-9139
keyword: infoeu-reposemanticsarticle
keyword: journal-articles
keyword: mesh-animals
keyword: mesh-carcinoma-hepatocellular
keyword: mesh-cell-differentiation
keyword: mesh-cell-line-tumor
keyword: mesh-epithelial-cells
keyword: mesh-hepatocyte-nuclear-factor-1-alpha
keyword: mesh-hepatocyte-nuclear-factor-4
keyword: mesh-hepatocytes
keyword: mesh-humans
keyword: mesh-liver-neoplasms
keyword: mesh-mesoderm
keyword: mesh-mice
keyword: mesh-mice-knockout
keyword: mesh-models-animal
keyword: mesh-phenotype
keyword: mesh-transcription-factors
keyword: sdvbclife-sciences-q-biocellular-biology
issued: 2026-05-05T14:18:12.025753
modified: 2026-05-05T14:18:12.025758
language: en
contact point: Organization
  fn: CCSD

test_moissonnage_selune
type: Agent

The stable repression of mesenchymal program is required for hepatocyte identity: a novel role for hepatocyte nuclear factor 4α.
type: Distribution
format: HTML
access URL: https://riip.hal.science/pasteur-00980177
issued: 2026-05-05T14:18:12.029914
modified: 2026-05-05T14:18:12.006498