ArticleGastroenterology2014
Extensive conversion of hepatic biliary epithelial cells to hepatocytes after near total loss of hepatocytes in zebrafish.
Article in Gastroenterology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers.
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Who cites it
136 citing papers in PubMed, 229 citations in OpenAlex.
- HMGB1 links chronic liver injury to progenitor responses and hepatocarcinogenesis.The Journal of clinical investigation · 2018Trial
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- Whole-organ single-cell mapping defines growth dynamics and clonal organization in developing and adult zebrafish livers.PLoS biology · 2026Article
- Solute Carrier Family 1 Member 5 (SLC1A5)-dependent glutamine transport regulates macrophage senescence and efferocytosis during liver regeneration.Molecular biomedicine · 2026Article
- Balancing Discovery and Caution: Regeneration in zebrafish toxicology.Current opinion in toxicology · 2026Article
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- SOX9 promotes hepatocyte proliferation via upregulating TGF-α expression during liver regeneration.Hepatology international · 2026Article
- A Novel Zebrafish Liver-Specific Metastasis Model Reveals c-Met as a Driver of Liver Tropism.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- CellCousin2: an optimized system for partial ablation and tracing of regenerative lineages.NPJ Regenerative medicine · 2026Article
- Massive hepatic necrosis-associated acute liver failure.eGastroenterology · 2026Review
- Liver Progenitor Cells: Cellular Origins, Plasticity, and Signaling Pathways in Liver Regeneration.Biology · 2025Review
- Triggering Mechanisms of Hepatocyte Repopulation during Liver Regeneration.Biomolecules & therapeutics · 2025Review
- Review
- Cholangiocytes contribute to hepatocyte regeneration after partial liver injury during growth spurt in zebrafish.Nature communications · 2025Article
- Khdrbs1 drives re-differentiation of bipotential progenitor cells by inhibiting p53 in zebrafish biliary-mediated liver regeneration.Development (Cambridge, England) · 2025Article
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Examining the liver-pancreas crosstalk reveals a role for the molybdenum cofactor in β-cell regeneration.Life science alliance · 2024Article
- Negative cell cycle regulation by calcineurin is necessary for proper beta cell regeneration in zebrafish.eLife · 2024Article
- Sex hormone receptors, calcium-binding protein and Yap1 signaling regulate sex-dependent liver cell proliferation following partial hepatectomy.Disease models & mechanisms · 2024Article
- Transdifferentiation is temporally uncoupled from progenitor pool expansion during hair cell regeneration in the zebrafish inner ear.Development (Cambridge, England) · 2024Article
76 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsBiliary epithelial cells (BECs) are considered to be a source of regenerating hepatocytes when hepatocyte proliferation is compromised. However, there is still controversy about the extent to which BECs can contribute to the regenerating hepatocyte population, and thereby to liver recovery. To investigate this issue, we established a zebrafish model of liver regeneration in which the extent of hepatocyte ablation can be controlled.
methodsHepatocytes were depleted by administration of metronidazole to Tg(fabp10a:CFP-NTR) animals. We traced the origin of regenerating hepatocytes using short-term lineage-tracing experiments, as well as the inducible Cre/loxP system; specifically, we utilized both a BEC tracer line Tg(Tp1:CreER(T2)) and a hepatocyte tracer line Tg(fabp10a:CreER(T2)). We also examined BEC and hepatocyte proliferation and liver marker gene expression during liver regeneration.
resultsBECs gave rise to most of the regenerating hepatocytes in larval and adult zebrafish after severe hepatocyte depletion. After hepatocyte loss, BECs proliferated as they dedifferentiated into hepatoblast-like cells; they subsequently differentiated into highly proliferative hepatocytes that restored the liver mass. This process was impaired in zebrafish wnt2bb mutants; in these animals, hepatocytes regenerated but their proliferation was greatly reduced.
conclusionsBECs contribute to regenerating hepatocytes after substantial hepatocyte depletion in zebrafish, thereby leading to recovery from severe liver damage.
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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.