Inactive

Alagille Syndrome (ALGS) is characterized by mutations in the JAG1 gene which lead to a variety of clinical symptoms, primarily bile duct paucity or the lack of proper bile duct formation. Hepatoblast... Alagille Syndrome (ALGS) is characterized by mutations in the JAG1 gene which lead to a variety of clinical symptoms, primarily bile duct paucity or the lack of proper bile duct formation. Hepatoblasts are bipotent cells that retain the ability to differentiate into either hepatocytes, the cell type that forms 85% of the liver, or cholangiocytes, the cells that form bile ducts. It is believed that haploinsufficiency of JAG1 affects this differentiation process resulting in a lack of cholangiocytes to form the growing bile duct network during fetal development. However, it is not clear if homogeneous (hepatoblast to hepatoblast) or heterogeneous (other cell to hepatoblast) JAG1 signaling is critical for this process. We aim to establish if homogeneous JAG1 signaling in patient-derived iPSC-generated hepatoblasts could drive differences in hepatoblast to cholangiocyte differentiation. To do this we will use RNA-seq to identify dysregulated pathways and biomarkers that should indicate if patient-derived hepatoblasts lack the ability to efficiently differentiate into cholangiocytes in comparison to control lines.