ArticleNature medicine2012
Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease.
Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 425 papers, 1 of them a synthesis that pooled it.
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
425 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Autologous macrophage therapy for liver cirrhosis: a phase 2 open-label randomized controlled trial.Nature medicine · 2025Trial
- Corneal macrophages and limbal stem cells: emerging roles in ocular surface regeneration.Annals of medicine · 2026Review
- Omics-based Decoding of Metabolic Dysfunction-associated Fatty Liver Disease: From Pathogenesis to Clinical Translation.Journal of clinical and translational hepatology · 2026Review
- Molecular mechanisms and pathogenesis of MASH.Nature · 2026Review
- MicroRNA Control of Hepatocyte-Stromal Crosstalk in the Early Premalignant Microenvironment of HBV-Associated HCC.International journal of molecular sciences · 2026Review
- The instructive scar - the dynamic role of extracellular matrix in biliary pathophysiology.Disease models & mechanisms · 2026Review
- TREM1-mediated macrophage activation drives voriconazole-induced hepatic steatosis: Diagnostic and therapeutic implications.Journal of pharmaceutical analysis · 2026Article
- Canonical WNT Ligands Produced by Regulatory T Cells Restrain Effector CD4bioRxiv : the preprint server for biology · 2026Article
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- Pediatric Cholestasis: A Practical Approach to Histological Diagnosis.Diagnostics (Basel, Switzerland) · 2026Review
- Wnt/β -catenin signalling shapes macrophage behaviour during injury and repair in the mouse submandibular gland.Scientific reports · 2026Article
- Gut microbiota dysbiosis contributes to diabetic nephropathy via affecting renal lipid deposition and inflammatory responses.Journal of translational medicine · 2026Article
- Iron-related intercellular communication in the liver: Main players and mechanisms.European journal of clinical investigation · 2026Review
- Macrophage polarization in ischemia-reperfusion injury: from molecular mechanisms to therapeutic strategies.Frontiers in immunology · 2026Review
- Postnatal Maxillofacial "Developing" Decellularized Extracellular Matrix Orchestrates Hierarchical Cross-Organ Regeneration via Macrophage Integrin αvβ5-Mediated Efferocytosis-Driven Developmental Recapitulation.Research (Washington, D.C.) · 2026Article
- Functional regulatory roles of HNF1B in promoting cell proliferation, migration, invasion and fate decision of hepatocellular carcinoma.BMC cancer · 2025Article
- Stem cell therapy: a novel frontier in the treatment of liver fibrosis/cirrhosis.Stem cell research & therapy · 2025Review
- Dual-ligand engineered exosome regulates WNT signaling activation to promote liver repair and regeneration.Nature communications · 2025Article
- Liver Progenitor Cells: Cellular Origins, Plasticity, and Signaling Pathways in Liver Regeneration.Biology · 2025Review
365 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors.
Funding
Abstract
During chronic injury a population of bipotent hepatic progenitor cells (HPCs) become activated to regenerate both cholangiocytes and hepatocytes. Here we show in human diseased liver and mouse models of the ductular reaction that Notch and Wnt signaling direct specification of HPCs via their interactions with activated myofibroblasts or macrophages. In particular, we found that during biliary regeneration, expression of Jagged 1 (a Notch ligand) by myofibroblasts promoted Notch signaling in HPCs and thus their biliary specification to cholangiocytes. Alternatively, during hepatocyte regeneration, macrophage engulfment of hepatocyte debris induced Wnt3a expression. This resulted in canonical Wnt signaling in nearby HPCs, thus maintaining expression of Numb (a cell fate determinant) within these cells and the promotion of their specification to hepatocytes. By these two pathways adult parenchymal regeneration during chronic liver injury is promoted.
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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.