ArticleStem cells translational medicine2026
JAG1 c.1615C > T mutation impairs bile duct regeneration but not differentiation in hepatic organoids derived from a patient with Alagille syndrome.
Article in Stem cells translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveAlagille syndrome (ALGS) is an autosomal dominant disorder caused primarily by mutations in JAG1. Intrahepatic bile duct paucity is the most consistently reported feature of ALGS; however, the mechanisms associated with biliary defects remain unclear.
methodsHere, we reverted or introduced the JAG1 c.1615C > T mutation to patient-specific induced pluripotent stem cells (iPSC) or human embryonic stem cells (hESCs) using base editors to generate isogenic cell lines and examine cellular phenotypes associated with this mutation in hepatic organoids.
resultsWe observed that JAG1 mutant lines showed no significant differences in cholangiocyte differentiation or function compared with the corresponding wild-type lines. By contrast, organoids derived from JAG1 mutant cells showed reduced cell survival, attenuated responsiveness to VEGF stimulation, and abnormal cell polarity.
conclusionsThese findings offer a new insight into the biliary pathologies in ALGS and provide theoretical support for future proof-of-concept studies of novel therapeutic approaches for ALGS.
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