Direct reprogramming into desired cell types by defined factors.

In the field of developmental biology, the concept that cells, once terminally differentiated, are fixed in their cell fate was long believed to be true. However, Dr. Gurdon and colleagues challenged this fundamental doctrine and demonstrated that cellular reprogramming and cell fate conversion are possible by somatic nuclear transfer and cell fusion. The Weintraub laboratory discovered in the 1980s that a single transcription factor, MyoD, can convert fibroblasts into skeletal muscle cells, and subsequent studies also demonstrated that several transcription factors are lineage converting factors within the blood cell lineage. In 2006, Takahashi and Yamanaka discovered that transduction of the four stem cell-specific transcription factors Oct4, Sox2, Klf4, and c-Myc can reprogram mouse fibroblast cells into a pluripotent state. In 2007, they demonstrated that the same four factors similarly reprogram human somatic cells into pluripotent stem cells. These discoveries by Dr. Yamanaka and colleagues fundamentally changed research in the fields of disease modeling and regenerative medicine and also inspired the next stage of cellular reprogramming, i.e., the generation of desired cell types without reverting to stem cells by overexpression of lineage-specific transcription factors. Recent studies demonstrated that a diverse range of cell types, such as pancreatic β cells, neurons, neural progenitors, cardiomyocytes, and hepatocytes, can be directly induced from somatic cells by combinations of specific factors. In this article, I review the pioneering works of cellular reprogramming and discuss the recent progress and future perspectives of direct reprogramming technology.