ArticleMolecular biology of the cell2007
Liver progenitor cells develop cholangiocyte-type epithelial polarity in three-dimensional culture.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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78 citing papers in PubMed, 166 citations in OpenAlex.
- Whole-organ single-cell mapping defines growth dynamics and clonal organization in developing and adult zebrafish livers.PLoS biology · 2026Article
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- E- and N-cadherin drive hepatic polarity and lumen elongation via opposing effects on RhoA activity.bioRxiv : the preprint server for biology · 2025Article
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- A TGFβ-ECM-integrin signaling axis drives structural reconfiguration of the bile duct to promote polycystic liver disease.Science translational medicine · 2023Article
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- Three-dimensional human bile duct formation from chemically induced human liver progenitor cells.Frontiers in bioengineering and biotechnology · 2023Article
- p53 positively regulates the proliferation of hepatic progenitor cells promoted by laminin-521.Signal transduction and targeted therapy · 2022Article
- Directing Cholangiocyte Morphogenesis in Natural Biomaterial Scaffolds.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Human Cholangiocytes Form a Polarized and Functional Bile Duct on Hollow Fiber Membranes.Frontiers in bioengineering and biotechnology · 2022Article
- Progress and Current Limitations of Materials for Artificial Bile Duct Engineering.Materials (Basel, Switzerland) · 2021Review
- Anisotropic expansion of hepatocyte lumina enforced by apical bulkheads.The Journal of cell biology · 2021Article
- Biofabricated 3D in vitro model of fibrosis-induced abnormal hepatoblast/biliary progenitors' expansion of the developing liver.Bioengineering & translational medicine · 2021Article
- Generation of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo.Nature communications · 2021Article
- Bile acid-activated macrophages promote biliary epithelial cell proliferation through integrin αvβ6 upregulation following liver injury.The Journal of clinical investigation · 2021Article
- Self-organization of organoids from endoderm-derived cells.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Cell-extracellular matrix interactions in the fluidic phase direct the topology and polarity of self-organized epithelial structures.Cell proliferation · 2021Article
- Prospect ofFrontiers in toxicology · 2021Review
18 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
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholangiocytes are cellular components of the bile duct system of the liver, which originate from hepatoblasts during embryonic liver development. Although several transcription factors and signaling molecules have been implicated in bile duct development, its molecular mechanism has not been studied in detail. Here, we applied a three-dimensional (3D) culture technique to a liver progenitor cell line, HPPL, to establish an in vitro culture system in which HPPL acquire differentiated cholangiocyte characteristics. When HPPL were grown in a gel containing Matrigel, which contains extracellular matrix components of basement membrane, HPPL developed apicobasal polarity and formed cysts, which had luminal space inside. In the cysts, F-actin bundles and atypical protein kinase C were at the apical membrane, E-cadherin was localized at the lateral membrane, and beta-catenin and integrin alpha6 were located at the basolateral membrane. HPPL in cysts expressed cholangiocyte markers, including cytokeratin 19, integrin beta4, and aquaporin-1, but not a hepatocyte marker, albumin. Furthermore, HPPL transported rhodamine 123, a substrate for multidrug resistance gene products, from the basal side to the central lumen. These data indicate that HPPL develop cholangiocyte-type epithelial polarity in 3D culture. Phosphatidylinositol 3-kinase signaling was essential for proliferation and survival of HPPL in culture, whereas laminin-1 was a crucial component of Matrigel for inducing epithelial polarization of HPPL. Because HPPL cysts display structural and functional similarities with bile ducts, the 3D culture of HPPL recapitulates in vivo cholangiocyte differentiation and is useful to study the molecular mechanism of bile duct development in vitro.
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