ArticleHepatology (Baltimore, Md.)2017
Bone morphogenetic protein signaling governs biliary-driven liver regeneration in zebrafish through tbx2b and id2a.
Article in Hepatology (Baltimore, Md.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 53 citations in OpenAlex.
- Massive hepatic necrosis-associated acute liver failure.eGastroenterology · 2026Review
- 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
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Deletion of Tgm2 suppresses BMP-mediated hepatocyte-to-cholangiocyte metaplasia in ductular reaction.Cell proliferation · 2024Article
- Review
- Determining Photoreceptor Cell Identity: Rod Versus Cone Fate Governed by tbx2b Opposing nrl.Investigative ophthalmology & visual science · 2024Article
- Using different zebrafish models to explore liver regeneration.Frontiers in cell and developmental biology · 2024Review
- PPARα activation promotes liver progenitor cell-mediated liver regeneration by suppressing YAP signaling in zebrafish.Scientific reports · 2023Article
- Arouse potential stemness: Intrinsic and acquired stem cell therapeutic strategies for advanced liver diseases.Cell insight · 2023Review
- Efficient knock-in method enabling lineage tracing in zebrafish.Life science alliance · 2023Article
- The MRN complex maintains the biliary-derived hepatocytes in liver regeneration through ATR-Chk1 pathway.NPJ Regenerative medicine · 2023Article
- Bipotent transitional liver progenitor cells contribute to liver regeneration.Nature genetics · 2023Article
- Update on Hepatobiliary Plasticity.Seminars in liver disease · 2023Article
- Biliary epithelial cells are facultative liver stem cells during liver regeneration in adult zebrafish.JCI insight · 2023Article
- Cellular crosstalk during liver regeneration: unity in diversity.Cell communication and signaling : CCS · 2022Review
- Article
- DNA methylation maintenance at the p53 locus initiates biliary-mediated liver regeneration.NPJ Regenerative medicine · 2022Article
- Premature Vertebral Mineralization inCells · 2022Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Upon mild liver injury, new hepatocytes originate from preexisting hepatocytes. However, if hepatocyte proliferation is impaired, a manifestation of severe liver injury, biliary epithelial cells (BECs) contribute to new hepatocytes through BEC dedifferentiation into liver progenitor cells (LPCs), also termed oval cells or hepatoblast-like cells (HB-LCs), and subsequent differentiation into hepatocytes. Despite the identification of several factors regulating BEC dedifferentiation and activation, little is known about factors involved in the regulation of LPC differentiation into hepatocytes during liver regeneration. Using a zebrafish model of near-complete hepatocyte ablation, we show that bone morphogenetic protein (Bmp) signaling is required for BEC conversion to hepatocytes, particularly for LPC differentiation into hepatocytes. We found that severe liver injury led to the up-regulation of genes involved in Bmp signaling, including smad5, tbx2b, and id2a, in the liver. Bmp suppression did not block BEC dedifferentiation into HB-LCs; however, the differentiation of HB-LCs into hepatocytes was impaired due to the maintenance of HB-LCs in an undifferentiated state. Later Bmp suppression did not affect HB-LC differentiation but increased BEC number through proliferation. Notably, smad5, tbx2b, and id2a mutants exhibited similar liver regeneration defects as those observed in Bmp-suppressed livers. Moreover, BMP2 addition promoted the differentiation of a murine LPC line into hepatocytes in vitro.
conclusionsBmp signaling regulates BEC-driven liver regeneration through smad5, tbx2b, and id2a: it regulates HB-LC differentiation into hepatocytes through tbx2b and BEC proliferation through id2a; our findings provide insights into promoting innate liver regeneration as a novel therapy. (Hepatology 2017;66:1616-1630).
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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.