ArticleScientific reports2016
Kupffer cells induce Notch-mediated hepatocyte conversion in a common mouse model of intrahepatic cholangiocarcinoma.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- Tissue-based detection of macrophage-associated YAP1-positive material in human acute liver injury: an exploratory immunopathological biopsy series.Diagnostic pathology · 2026Article
- Preclinical mouse models for studying cholangiocarcinoma.Liver research (Beijing, China) · 2026Review
- The oncogenic potential of YAP requires Y357 phosphorylation in cholangiocytes but not in hepatocytes.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Diverse functions of SOX9 in liver development and homeostasis and hepatobiliary diseases.Genes & diseases · 2024Review
- A Novel Mouse Model of Intrahepatic Cholangiocarcinoma Induced by Azoxymethane.International journal of molecular sciences · 2023Article
- Analysis of viral integration reveals new insights of oncogenic mechanism in HBV-infected intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma.Hepatology international · 2022Article
- Role of Immune Cells in Biliary Repair.Frontiers in immunology · 2022Review
- The crosstalk between parenchymal cells and macrophages: A keeper of tissue homeostasis.Frontiers in immunology · 2022Review
- Genomic characterization of rare molecular subclasses of hepatocellular carcinoma.Communications biology · 2021Article
- Notch signalling pathway in development of cholangiocarcinoma.World journal of gastrointestinal oncology · 2020Review
- Myofibroblast induces hepatocyte-to-ductal metaplasia via laminin-ɑvβ6 integrin in liver fibrosis.Cell death & disease · 2020Article
- Liver Progenitors and Adult Cell Plasticity in Hepatic Injury and Repair: Knowns and Unknowns.Annual review of pathology · 2020Review
- Hepatic Macrophages in Liver Injury.Frontiers in immunology · 2020Review
- Cholangiocarcinoma: Classification, Histopathology and Molecular Carcinogenesis.Pathology oncology research : POR · 2020Review
- Translational Bioinformatics for Cholangiocarcinoma: Opportunities and Challenges.International journal of biological sciences · 2018Review
- Identification of a novel alpha-fetoprotein-expressing cell population induced by the Jagged1/Notch2 signal in murine fibrotic liver.Hepatology communications · 2017Article
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8 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a malignant epithelial neoplasm composed of cells resembling cholangiocytes that line the intrahepatic bile ducts in portal areas of the hepatic lobule. Although ICC has been defined as a tumor arising from cholangiocyte transformation, recent evidence from genetic lineage-tracing experiments has indicated that hepatocytes can be a cellular origin of ICC by directly changing their fate to that of biliary lineage cells. Notch signaling has been identified as an essential factor for hepatocyte conversion into biliary lineage cells at the onset of ICC. However, the mechanisms underlying Notch signal activation in hepatocytes remain unclear. Here, using a mouse model of ICC, we found that hepatic macrophages called Kupffer cells transiently congregate around the central veins in the liver and express the Notch ligand Jagged-1 coincident with Notch activation in pericentral hepatocytes. Depletion of Kupffer cells prevents the Notch-mediated cell-fate conversion of hepatocytes to biliary lineage cells, inducing hepatocyte apoptosis and increasing mortality in mice. These findings will be useful for uncovering the pathogenic mechanism of ICC and developing prevenient and therapeutic strategies for this refractory disease.
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