Direct lineage conversion of fibroblasts to hepatocyte-like cells

Abstract

Generation of expandable patient-specific hepatocytes has great potentials in treating liver diseases and drug screening. Here, I report that hepatocytes can be induced from mouse tail-tip fibroblasts (TTF) by lentiviral-mediated delivery of Oct4 and Hnf4α. Induced hepatocytes (iHep) show typical cubic morphology, acquire hepatic markers and functions, including glycogen storage, low-density lipoprotein uptake and indocyanine green metabolism, and cytochrome P450 enzyme induction. Transplanted iHep cells successfully engraft and may contribute to the reduction of inflammation response in carbon tetrachloride (CCl4)-induced mouse model. This study demonstrates a novel set of transcription factors in converting fibroblasts into functional hepatocytes with potential pharmaceutical applications.