ArticleJCI insight2023
Biliary epithelial cells are facultative liver stem cells during liver regeneration in adult zebrafish.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- UHRF1 overexpression generates distinct senescent states with different Tp53 dependencies.EMBO reports · 2026Article
- TGF-β serves as a critical signaling determinant of liver progenitor cell activation and function.The Journal of clinical investigation · 2026Article
- Whole-organ single-cell mapping defines growth dynamics and clonal organization in developing and adult zebrafish livers.PLoS biology · 2026Article
- Niche-dependent modular regulation of the stem cell transcriptome separates cell identity and potential.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- CellCousin2: an optimized system for partial ablation and tracing of regenerative lineages.NPJ Regenerative medicine · 2026Article
- Article
- Rewinding the clock: mechanisms of dedifferentiation.Current opinion in genetics & development · 2025Review
- Triggering Mechanisms of Hepatocyte Repopulation during Liver Regeneration.Biomolecules & therapeutics · 2025Review
- Cholangiocytes contribute to hepatocyte regeneration after partial liver injury during growth spurt in zebrafish.Nature communications · 2025Article
- Zebrafish as a model for human epithelial pathology.Laboratory animal research · 2025Review
- New Progress in Zebrafish Liver Tumor Models: Techniques and Applications in Hepatocellular Carcinoma Research.International journal of molecular sciences · 2025Review
- Epigenetic Disordering Drives Stemness, Senescence Escape and Tumor Heterogeneity.bioRxiv : the preprint server for biology · 2024Article
- Establishment and long-term expansion of adult hepatobiliary organoids co-cultured with liver endothelial cells.Heliyon · 2024Article
- Origins of cancer: ain't it just mature cells misbehaving?The EMBO journal · 2024Review
- Metabolic inflexibility promotes mitochondrial health during liver regeneration.Science (New York, N.Y.) · 2024Article
- Using different zebrafish models to explore liver regeneration.Frontiers in cell and developmental biology · 2024Review
- Fishing Innate Immune System Properties through the Transcriptomic Single-Cell Data ofBiology · 2023Review
- VEGFA mRNA-LNP promotes biliary epithelial cell-to-hepatocyte conversion in acute and chronic liver diseases and reverses steatosis and fibrosis.Cell stem cell · 2023Article
- PPARα activation promotes liver progenitor cell-mediated liver regeneration by suppressing YAP signaling in zebrafish.Scientific reports · 2023Article
- Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.