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
  • Animals
  • Biliary Tract*
  • Hepatocytes
  • Liver
  • Liver Regeneration*/physiology
  • Repressor Proteins
  • Stem Cells
  • Zebrafish/physiology
  • Zebrafish Proteins/genetics
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
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes