The present results expand the existing evidence, including murine CCA models generated by AKT/NICD [40], AKT/YAP [37], AKT/Jagged1 [34], and AKT/Fbxw7ΔF [48] mice, that the canonical Notch pathway is responsible for biliary commitment in mouse tumors induced by hydrodynamic gene delivery. Here, NOTCH1 is linked to cholangiocarcinoma.