Cell fate modification toward the hepatic lineage by extrinsic factors

The lineage of a somatic cell can be altered by targeting its signaling networks with small molecules and/or genetically altering the expression of key transcription factors. Depending on the combination of factors, fibroblasts can be fully reprogrammed into induced pluripotent stem (iPS) cells or directly converted into specific cell lineages, bypassing the pluripotent state. The generation of defined target cells will enormously benefit patients who require cell transplantation therapy. In the decade, since iPS cells were first generated, many cell types have been induced from fibroblasts by direct conversion, including hepatocytes. Converted hepatocyte-like cells have been shown to repopulate liver tissues after transplantation in mouse liver disease models, suggesting promise for future application in humans. Thus, to realize safe and efficient cell transplantation therapy, various methods for generating hepatocyte-like cells are being developed. In this review, we summarize the current methods for the generation of hepatocyte-like cells via cell fate modification using extrinsic factors.