Direct reprogramming of mouse fibroblasts into functional hepatocytes

This protocol describes the direct reprogramming of fibroblasts into induced hepatocyte-like cells by expression of Hnf4a and one of the following genes: Foxa1, Foxa2, or Foxa3. The induced hepatocyte-like cells express hepatocyte and epithelium-specific markers. In order to check their functionality in-vivo, the cells were transplanted into Fag knockout mice, an established animal model for hereditary tyrosinemia type 1. At one month post-transplantation, the cells were shown to engraft and successfully reconstitute the recipient's hepatic tissue.