The overall goal of the research funded by this award was to establish the feasibility of generating therapeutically effective human hepatocytes in the laboratory. Another goal was to generate these hepatocytes so that they would not require immune suppression after transplantation. For this we investigated how hepatocyte differentiation and proliferation are regulated in mice and humans and applied this insight for the directed differentiation of human fibroblasts fully or partially reprogrammed to pluripotency. Our results showed that human fibroblasts can be converted into cells that replicate both function and proliferation of primary human hepatocytes, thereby establishing the feasibility of autologous liver cell therapy not requiring immune suppression.