Direct Reprogramming of Somatic Cells to a Pluripotent State

Somatic cell reprogramming is the process of converting the epigenetic state of a differentiated somatic cell into a pluripotent state capable of giving rise to any cell type. Due to this ability to differentiate into all somatic cell types, pluripotent stem cells bear promise to advance biomedical research and regenerative medicine. Transplantation of specific functional cell types to replenish lost tissue has been proposed as a strategy to treat degenerative diseases such as Parkinson's disease, diabetes, and heart disease. For such therapies, the use of patient-derived cells generated by re-programming is advantageous over conventional embryonic stem cells, as autologous cells are predicted to evade immune rejection upon transplantation. One of the strategies proposed to generate patient-derived pluripotent cells is the transfer of a somatic nucleus into a human donor oocyte. This procedure, termed somatic cell nuclear transfer (SCNT), was successfully used to generate live cloned animals from terminally differentiated somatic nuclei. Cells derived by direct reprogramming, termed induced pluripotent stem cells (iPSCs), share all the key characteristics of ES cells. Since the first derivation of iPSCs, experimental efforts have focused on developing better tools to investigate and streamline the reprogramming process which include optimizing the delivery of the reprogramming factors into somatic cells, improving reprogramming efficiency, determining the cell types amenable to direct reprogramming, and identifying potential intermediate cell states during the reprogramming process. Major efforts have been made to bring iPSC technology towards a therapeutic application.