The rebirth of iPSCs: Towards a healthier epigenetic landscape

It is well recognized that transcription factor-induced iPSCs carry an aberrant genetic and epigenetic makeup. However, it is not clear whether these defects are developed de novo due to the reprogramming process or inherited from the somatic source cells. Ma and colleagues presented convincing data that iPSCs derived through transcription factor over-expression carry a higher incidence of the epigenetic flaws in comparison with those generated through SCNT. The authors conclude that 1) the source of the epigenetic aberrations is more related to the reprogramming protocol, and less to the intrinsic abnormality of the somatic source cells; 2) SCNT based protocol is superior to that involving a cocktail of transcription factors. These important findings by Ma and colleagues will certainly steer future research towards understanding the mechanisms underpinning the SCNT reprogramming. With these efforts a whole array of unknown factors is expected to emerge, which regulate the onset of early embryonic development and can be applied to induce iPSCs with a healthier epigenetic landscape.