Cellular reprogramming and fate conversion

Cellular reprogramming and fate conversion have long been recognized in somatic nuclear transfer and cell fusion experiments. The potency of specific transcription factors as cell fate determinants was first demonstrated by the discovery of MyoD, a master gene for skeletal muscle differentiation, and by the subsequent identification of several genes as lineage-converting factors within the blood cell lineage. These pioneer works led to the landmark study by Dr. Yamanaka and colleagues in 2006 that is reprogramming of somatic cells into a pluripotent state by transduction of the four stem cell-specific transcription factors, Oct4, Sox2, Klf4, and c-Myc. This study fundamentally altered the approach to regenerative medicine and also inspired a broad strategy to generate desired cell types by introducing combinations of lineage-specific transcription factors. In fact, it has been demonstrated that a diverse range of cell types, such as pancreatic β cells, neurons, cardiomyocytes, and hepatocytes, could be directly induced from heterologous cells by combinations of lineage-specific reprogramming factors. This chapter reviews the pioneer and recent works of cellular reprogramming and fate conversion, and also discusses the future perspective and challenges of using this technology in regenerative medicine.