PUBLICATION
Biliary epithelial cells are facultative liver stem cells during liver regeneration in adult zebrafish
- Authors
- Oderberg, I.M., Goessling, W.
- ID
- ZDB-PUB-230111-2
- Date
- 2023
- Source
- JCI insight 8(1): (Journal)
- Registered Authors
- Goessling, Wolfram
- Keywords
- Adult stem cells, Hepatology, Stem cells
- Datasets
- GEO:GSE217839
- MeSH Terms
-
- Animals
- Epithelial Cells
- Liver
- Liver Regeneration*/physiology
- Phosphatidylinositol 3-Kinases
- Stem Cells
- TOR Serine-Threonine Kinases
- Zebrafish*
- PubMed
- 36625346 Full text @ JCI Insight
Citation
Oderberg, I.M., Goessling, W. (2023) Biliary epithelial cells are facultative liver stem cells during liver regeneration in adult zebrafish. JCI insight. 8(1):.
Abstract
The liver is a highly regenerative organ, yet the presence of a dedicated stem cell population remains controversial. Here, we interrogate a severe hepatocyte injury model in adult zebrafish to define that regeneration involves a stem cell population. After near-total hepatocyte ablation, single-cell transcriptomic and high-resolution imaging analyses throughout the entire regenerative timeline reveal that biliary epithelial cells undergo transcriptional and morphological changes to become hepatocytes. As a population, biliary epithelial cells give rise to both hepatocytes and biliary epithelial cells. Biliary epithelial cells proliferate and dedifferentiate to express hepatoblast transcription factors prior to hepatocyte differentiation. This process is characterized by increased MAPK, PI3K, and mTOR signaling, and chemical inhibition of these pathways impairs biliary epithelial cell proliferation and fate conversion. We conclude that, upon severe hepatocyte ablation in the adult liver, biliary epithelial cells act as facultative liver stem cells in an EGFR-PI3K-mTOR-dependent manner.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping