ArticleGenes & development2013
Specific fate decisions in adult hepatic progenitor cells driven by MET and EGFR signaling.
Article in Genes & development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 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
57 citing papers in PubMed, 110 citations in OpenAlex.
- TGF-β serves as a critical signaling determinant of liver progenitor cell activation and function.The Journal of clinical investigation · 2026Article
- Interplay among oncogenic pathways governs hepatobiliary lineage decisions in liver cancer.iLIVER · 2026Article
- Effect of 2D and 3D ECM and Biomechanical Cues on Human iPSC-Derived Liver Progenitor Cell Differentiation.Advanced healthcare materials · 2026Article
- Liver Progenitor Cells: Cellular Origins, Plasticity, and Signaling Pathways in Liver Regeneration.Biology · 2025Review
- Liver oval cells in response to HDAC1 inhibitor trichostatin A: immunohistochemical characterization using OV-6 hepatic expression.Anatomy & cell biology · 2025Article
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- The Potential Hepatocyte Differentiation Targets and MSC Proliferation by FH1.Journal of cellular and molecular medicine · 2025Article
- Regenerative human liver organoids (HLOs) in a pillar/perfusion plate for hepatotoxicity assays.bioRxiv : the preprint server for biology · 2024Article
- Liver organoids: updates on generation strategies and biomedical applications.Stem cell research & therapy · 2024Review
- Liver regeneration after injury: Mechanisms, cellular interactions and therapeutic innovations.Clinical and translational medicine · 2024Review
- Review
- GITRL impairs hepatocyte repopulation by liver progenitor cells to aggravate inflammation and fibrosis by GITRCell death & disease · 2024Article
- Uncovering a Novel Functional Interaction Between Adult Hepatic Progenitor Cells, Inflammation and EGFR Signaling During Bile Acids-Induced Injury.International journal of biological sciences · 2024Article
- Delineating cooperative effects of Notch and biomechanical signals on patterned liver differentiation.Communications biology · 2022Article
- Beta-carotene regulates the biological activity of EGF in IEC6 cells by alleviating the inflammatory process.Cell cycle (Georgetown, Tex.) · 2022Article
- Cellular origins of regenerating liver and hepatocellular carcinoma.JHEP reports : innovation in hepatology · 2022Review
- Wnt signaling in biliary development, proliferation, and fibrosis.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- Article
- Biliary organoids uncover delayed epithelial development and barrier function in biliary atresia.Hepatology (Baltimore, Md.) · 2022Observational
- Generation of In Vivo Traceable Hepatocyte-Like Cells from Human iPSCs.Methods in molecular biology (Clifton, N.J.) · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
The relative contribution of hepatocyte growth factor (HGF)/MET and epidermal growth factor (EGF)/EGF receptor (EGFR), two key signal transduction systems in the normal and diseased liver, to fate decisions of adult hepatic progenitor cells (HPCs) has not been resolved. Here, we developed a robust culture system that permitted expansion and genetic manipulation of cells capable of multilineage differentiation in vitro and in vivo to examine the individual roles of HGF/MET and EGF/EGFR in HPC self-renewal and binary cell fate decision. By employing loss-of-function and rescue experiments in vitro, we showed that both receptors collaborate to increase the self-renewal of HPCs through activation of the extracellular signal-regulated kinase (ERK) pathway. MET was a strong inducer of hepatocyte differentiation by activating AKT and signal transducer and activator of transcription (STAT3). Conversely, EGFR selectively induced NOTCH1 to promote cholangiocyte specification and branching morphogenesis while concomitantly suppressing hepatocyte commitment. Furthermore, unlike the deleterious effects of MET deletion, the liver-specific conditional loss of Egfr facilitated rather than suppressed progenitor-mediated liver regeneration by switching progenitor cell differentiation toward hepatocyte lineage. These data provide new insight into the mechanisms regulating the stemness properties of adult HPCs and reveal a previously unrecognized link between EGFR and NOTCH1 in directing cholangiocyte differentiation.
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What OpenQuestion holds
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.