PUBLICATION
Khdrbs1 drives redifferentiation of bipotential progenitor cell by inhibiting p53 in zebrafish biliary-mediated liver regeneration
- Authors
- Gang, K., Chen, Q., Sun, J., Zhang, T., Cai, P., Ni, R., Ma, J.
- ID
- ZDB-PUB-250218-15
- Date
- 2025
- Source
- Development (Cambridge, England) : (Journal)
- Registered Authors
- Ma, Jianlong
- Keywords
- Sam68, Biliary epithelial cell, Cell proliferation, Liver injury, Transdifferentiation
- MeSH Terms
-
- Signal Transduction
- RNA-Binding Proteins/genetics
- RNA-Binding Proteins/metabolism
- Stem Cells*/cytology
- Stem Cells*/metabolism
- Liver Regeneration*/genetics
- Cell Differentiation*/genetics
- Liver/cytology
- Liver/metabolism
- Animals
- Hepatocytes/cytology
- Hepatocytes/metabolism
- Tumor Suppressor Protein p53*/genetics
- Tumor Suppressor Protein p53*/metabolism
- Biliary Tract/cytology
- Biliary Tract/metabolism
- Cell Proliferation/genetics
- Zebrafish*/genetics
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Epithelial Cells/cytology
- Epithelial Cells/metabolism
- PubMed
- 39963927 Full text @ Development
Citation
Gang, K., Chen, Q., Sun, J., Zhang, T., Cai, P., Ni, R., Ma, J. (2025) Khdrbs1 drives redifferentiation of bipotential progenitor cell by inhibiting p53 in zebrafish biliary-mediated liver regeneration. Development (Cambridge, England). :.
Abstract
After severe liver injury, biliary epithelial cells (BECs) undergo dedifferentiation into bipotential progenitor cells (BPPCs), which subsequently redifferentiate into nascent hepatocytes and BECs to accomplish liver regeneration. However, the critical factors governing the redifferentiation process of BPPCs remain largely unknown. Here, using a zebrafish model of severe liver injury, we observed specific expression of khdrbs1a and khdrbs1b (collectively known as khdrbs1) in BPPCs through single-cell RNA analyses and fluorescence in situ hybridization. Subsequently, to eliminate the genetic compensation, we generated a CRISPR/dead Cas9-mediated system for interfering khdrbs1 in BECs, which caused the defective liver regeneration and impaired redifferentiation of BPPCs. Furthermore, the khdrbs1-/- mutant displayed impaired proliferation and redifferentiation of BPPCs during liver regeneration. Mechanistically, p53 signaling was activated in response to the loss of khdrbs1, and tp53 mutation partially rescued the defective liver regeneration of the khdrbs1-/- mutant. In summary, we elucidate that Khdrbs1 promotes the redifferentiation of BPPCs in part by inhibiting p53 activation during biliary-mediated liver regeneration in zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping