ArticleStem cells translational medicine2024
Effect of Valproic Acid on Promoting the Differentiation of Human Embryonic Stem Cells Into Cholangiocyte-Like Cells.
Article in Stem cells translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 3 citations in OpenAlex.
- Aquaporin membrane channels in the hepatobiliary tract: a model of complexity and clinical implications in health and disease.Internal and emergency medicine · 2026Review
- Amelioration of biased neuronal differentiation in humanized mouse model of valproic acid-induced autism by precisely targeted transcranial magnetic stimulation.Bioengineering & translational medicine · 2025Article
- Chemically Defined Organoid Culture System for Cholangiocyte Differentiation.Advanced healthcare materials · 2024Article
- Aquaporins in Biliary Function: Pathophysiological Implications and Therapeutic Targeting.International journal of molecular sciences · 2024Review
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Cholangiocytes form a complex 3D network of bile ducts in the liver and contribute to liver function. The damage or destruction of cholangiocytes can lead to biliary diseases, and the shortage of cholangiocytes remains an obstacle for drug development targeting biliary diseases. Valproic acid (VPA) is a potent activator of Notch signaling pathway that is essential for cholangiocyte differentiation. Here, we report a VPA-based approach for cholangiocyte differentiation of human pluripotent stem cells. VPA activated Notch2 expression and upregulated HES-1, HEY-1, and Sox9 gene expression in hESC-derived hepatoblast. After 7 days treatment, VPA promoted successful differentiation of hepatoblast into cholangiocytes expressing cholangiocyte marker genes (AE2, AQP1, CFTR) and proteins (CK19 and CK7). In addition, the differentiated cholangiocytes formed bile duct-like structures after implantation into the spleen of NOD/SCID mice. Our results suggested that VPA can promote hESC differentiation to cholangiocyte-like cells. The induced cholangiocytes may serve as a potential cell source for both in vitro modeling and regenerative therapy of cholangiopathies. The findings can also support further development of small-molecule based differentiation protocols for cholangiocyte production.
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Registered trials
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