PUBLICATION
Tel2 regulates redifferentiation of bipotential progenitor cells via Hhex during zebrafish liver regeneration
- Authors
- Zhang, J., Zhou, Y., Li, S., Mo, D., Ma, J., Ni, R., Yang, Q., He, J., Luo, L.
- ID
- ZDB-PUB-220407-4
- Date
- 2022
- Source
- Cell Reports 39: 110596 (Journal)
- Registered Authors
- He, Jianbo, Luo, Lingfei
- Keywords
- CP: Cell biology, biliary epithelial cell, hhex, liver, tel2, transdifferentiation
- MeSH Terms
-
- Zebrafish Proteins/genetics
- Animals
- Liver
- Repressor Proteins
- Zebrafish/physiology
- PubMed
- 35385752 Full text @ Cell Rep.
Abstract
Upon extensive hepatocyte loss or impaired hepatocyte proliferation, liver regeneration occurs via biliary epithelial cell (BEC) transdifferentiation, which includes dedifferentiation of BECs into bipotential progenitor cells (BP-PCs) and then redifferentiation of BP-PCs to nascent hepatocytes and BECs. This BEC-driven liver regeneration involves reactivation of hepatoblast markers, but the underpinning mechanisms and their effects on liver regeneration remain largely unknown. Using a zebrafish extensive hepatocyte ablation model, we perform an N-ethyl-N-nitrosourea (ENU) forward genetic screen and identify a liver regeneration mutant, liver logan (lvl), in which the telomere maintenance 2 (tel2) gene is mutated. During liver regeneration, the tel2 mutation specifically inhibits transcriptional activation of a hepatoblast marker, hematopoietically expressed homeobox (hhex), in BEC-derived cells, which blocks BP-PC redifferentiation. Mechanistic studies show that Tel2 associates with the hhex promoter region and promotes hhex transcription. Our results reveal roles of Tel2 in the BP-PC redifferentiation process of liver regeneration by activating hhex.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping