Although several recent reports suggest the possibility that ICC can arise from hepatocytes through Notch-mediated transdifferentiation29, 30, we have demonstrated, using cholangiocyte- or hepatocyte-specific Cre-loxP system, that ICCs in this model originated from cholangiocytes that were differentiated from Kras activated and Pten deleted progenitor cells. This evidence concerns the gene PTEN and intrahepatic cholangiocarcinoma.