PUBLICATION
Cholangiocytes contribute to hepatocyte regeneration after partial liver injury during growth spurt in zebrafish
- Authors
- Eski, S.E., Mi, J., Pozo-Morales, M., Hovhannisyan, G.G., Perazzolo, C., Manco, R., Ez-Zammoury, I., Barbhaya, D., Lefort, A., Libert, F., Marini, F., Gurzov, E.N., Andersson, O., Singh, S.P.
- ID
- ZDB-PUB-250608-5
- Date
- 2025
- Source
- Nature communications 16: 52605260 (Journal)
- Registered Authors
- Eski, Sema Elif, Perazzolo, Camille, Pozo‐Morales, Macarena, Singh, Sumeet Pal
- Keywords
- none
- Datasets
- GEO:GSE272484
- MeSH Terms
-
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Liver*/cytology
- Liver*/injuries
- Liver*/metabolism
- Animals
- Hepatectomy
- Epithelial Cells*/cytology
- Epithelial Cells*/metabolism
- Cell Transdifferentiation
- Single-Cell Analysis
- Hepatocytes*/cytology
- Hepatocytes*/metabolism
- Hepatocytes*/physiology
- Liver Regeneration*/physiology
- Bile Ducts/cytology
- Zebrafish*/growth & development
- Signal Transduction
- Mechanistic Target of Rapamycin Complex 1/metabolism
- PubMed
- 40480975 Full text @ Nat. Commun.
Citation
Eski, S.E., Mi, J., Pozo-Morales, M., Hovhannisyan, G.G., Perazzolo, C., Manco, R., Ez-Zammoury, I., Barbhaya, D., Lefort, A., Libert, F., Marini, F., Gurzov, E.N., Andersson, O., Singh, S.P. (2025) Cholangiocytes contribute to hepatocyte regeneration after partial liver injury during growth spurt in zebrafish. Nature communications. 16:52605260.
Abstract
The liver's regenerative ability depends on injury extent. Minor injuries are repaired by hepatocyte self-duplication, while severe damage triggers cholangiocyte involvement in hepatocyte recovery. This paradigm is well-documented for adult animals but is less explored during rapid growth. We design two partial liver injury models in zebrafish, which were investigated during growth spurts: 1) partial ablation, killing half the hepatocytes; and 2) partial hepatectomy, removing half a liver lobe. In both injuries, de novo hepatocytes emerged alongside existing ones. Single-cell transcriptomics and lineage tracing with Cre-driver lines generated by genome editing identified cholangiocytes as the source of de novo hepatocytes. We further identify active mTORC1 signalling in the uninjured liver of growing animal to be a regulator of the enhanced plasticity of cholangiocytes. Our study suggests cholangiocyte-to-hepatocyte transdifferentiation as the primary mechanism of liver regeneration during periods of rapid growth.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping