# Transcriptional Control: A Directional Sign at the Crossroads of Adult Hepatic Progenitor Cells' Fates

## TL;DR

This paper explores how transcription factors control the fate of liver progenitor cells and their role in liver regeneration and tumor formation.

## Contribution

The paper identifies specific transcription factors and their regulatory roles in adult hepatic progenitor cell fate and tumor predisposition.

## Key findings

- Transcription factors like FoxA1/2/3, YB-1, and HNF4α regulate hepatic progenitor cell differentiation and plasticity.
- Dysregulation of these factors increases tumor predisposition in adult hepatic progenitor cells.
- Altered differentiation pathways of HPCs may contribute to intrahepatic tumor development.

## Abstract

Hepatic progenitor cells (HPCs) have a bidirectional potential to differentiate into hepatocytes and bile duct epithelial cells and constitute a second barrier to liver regeneration in the adult liver. They are usually located in the Hering duct in the portal vein region where various cells, extracellular matrix, cytokines, and communication signals together constitute the niche of HPCs in homeostasis to maintain cellular plasticity. In various types of liver injury, different cellular signaling streams crosstalk with each other and point to the inducible transcription factor set, including FoxA1/2/3, YB-1, Foxl1, Sox9, HNF4α, HNF1α, and HNF1β. These transcription factors exert different functions by binding to specific target genes, and their products often interact with each other, with diverse cascades of regulation in different molecular events that are essential for homeostatic regulation, self-renewal, proliferation, and selective differentiation of HPCs. Furthermore, the tumor predisposition of adult HPCs is found to be significantly increased under transcriptional factor dysregulation in transcriptional analysis, and the altered initial commitment of the differentiation pathway of HPCs may be one of the sources of intrahepatic tumors. Related transcription factors such as HNF4α and HNF1 are expected to be future targets for tumor treatment.