ArticleThe Journal of clinical investigation2015
Lineage fate of ductular reactions in liver injury and carcinogenesis.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
101 citing papers in PubMed, 148 citations in OpenAlex.
- HMGB1 links chronic liver injury to progenitor responses and hepatocarcinogenesis.The Journal of clinical investigation · 2018Trial
- MAP2-mediated integrin dysregulation reprograms cancer cell plasticity in hepatocellular carcinoma.Nature communications · 2026Article
- ICMT deficiency ameliorates weight loss and mortality, but not tumor formation in a mouse model of liver cancer.Cell communication and signaling : CCS · 2026Article
- Massive hepatic necrosis-associated acute liver failure.eGastroenterology · 2026Review
- [The logic of survival in patients with acute liver failure].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Microenvironmental control of the ductular reaction: balancing repair and disease progression.Cell death & disease · 2025Review
- Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities.Gastroenterology · 2025Review
- Application of mesenchymal stem cells in liver fibrosis and regeneration.Liver research (Beijing, China) · 2024Review
- HBV-related HCC development in mice is STAT3 dependent and indicates an oncogenic effect of HBx.JHEP reports : innovation in hepatology · 2024Article
- Aberrant differentiation and proliferation of hepatocytes in chronic liver injury and liver tumors.Pathology international · 2024Review
- Cancer stem cell-immune cell crosstalk in the tumor microenvironment for liver cancer progression.Frontiers of medicine · 2024Review
- Smad4 restricts injury-provoked biliary proliferation and carcinogenesis.Disease models & mechanisms · 2024Article
- A spatiotemporal atlas of cholestatic injury and repair in mice.Nature genetics · 2024Article
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) deletion in myeloid cells augments cholestatic liver injury.Scientific reports · 2024Article
- SPINK1-induced tumor plasticity provides a therapeutic window for chemotherapy in hepatocellular carcinoma.Nature communications · 2023Article
- Panic at the Bile Duct: How Intrahepatic Cholangiocytes Respond to Stress and Injury.The American journal of pathology · 2023Review
- NOTCH signalling - a core regulator of bile duct disease?Disease models & mechanisms · 2023Review
- Significance of CCNs in liver regeneration.Journal of cell communication and signaling · 2023Review
- The Synergistic Effect of Interventional Locoregional Treatments and Immunotherapy for the Treatment of Hepatocellular Carcinoma.International journal of molecular sciences · 2023Review
- Bipotent transitional liver progenitor cells contribute to liver regeneration.Nature genetics · 2023Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
Ductular reactions (DRs) are observed in virtually all forms of human liver disease; however, the histogenesis and function of DRs in liver injury are not entirely understood. It is widely believed that DRs contain bipotential liver progenitor cells (LPCs) that serve as an emergency cell pool to regenerate both cholangiocytes and hepatocytes and may eventually give rise to hepatocellular carcinoma (HCC). Here, we used a murine model that allows highly efficient and specific lineage labeling of the biliary compartment to analyze the histogenesis of DRs and their potential contribution to liver regeneration and carcinogenesis. In multiple experimental and genetic liver injury models, biliary cells were the predominant precursors of DRs but lacked substantial capacity to produce new hepatocytes, even when liver injuries were prolonged up to 12 months. Genetic modulation of NOTCH and/or WNT/β-catenin signaling within lineage-tagged DRs impaired DR expansion but failed to redirect DRs from biliary differentiation toward the hepatocyte lineage. Further, lineage-labeled DRs did not produce tumors in genetic and chemical HCC mouse models. In summary, we found no evidence in our system to support mouse biliary-derived DRs as an LPC pool to replenish hepatocytes in a quantitatively relevant way in injury or evidence that DRs give rise to HCCs.
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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.