During developmental differentiation or programming, different cell types acquire distinct epigenetic profiles mediated by transcription factors (TF) and epigenetic modifications. In this figure, the epigenetic code is reflected by modifications of histones associated with gene activation (Ac, acetylation; H3K9Ac, acetylation of histone H3 at lysine 9; H3K4Me, methylation of histone 3 at lysine 4) or repression (H3K9Me and H3K27Me, methylation of histone H3 at lysine 9 and 27, respectively) and by methylation of CpG dinucleotides. Developmental programming results in somatic cells that exhibit decreased pluripotency. Reprogramming, achieved by exogenous expression of transcription factors, allows for a cell to switch from an epigenome of usually reduced potency to one of pluripotency. Open circles represent unmethylated CpGs; filled circles represent methylated CpGs.

The choice of the cell type from which to derive iPS cells, the choice of reprogramming factors and methods of delivery, as well as evaluation of iPS cell progeny, will depend on the potential application of the resulting cell types.

iPS cell technology has exciting potential applications in disease modeling and drug discovery. Cell replacement therapy with healthy iPS cell–derived cells is also a possible future development. Genetic mutations can be targeted by gene therapy approaches before or after reprogramming.