The reprogramming process involves the re-activation of key genes in the somatic cell, that are important in normal embryonic stem cells to maintain their characteristic pluripotent state. This is a highly specific, inefficient, and intricate processes triggered by introduction of a set of key transcription factors required to dedifferentiate a somatic cell into an hiPSC, a process which leads to a unique “open” chromatin profile (Box 1) 27–31. The efficiency of this process is influenced by many other factors including bioenergetic factors, cell cycle regulators and microRNAs 32 as well as dosage of reprogramming factors 33. Far less is understood about establishing and maintaining a pluripotency circuitry than is understood about the initial reprogramming step. What is known is that several new genes are activated and consequently several developmental transcription factor cascades turned on. We refer the reader to an excellent review by Buganim et al. for a more in-depth discussion of the subject 34. This process is far from perfect and hiPSCs may still retain some of their originator somatic cell’s gene expression patterns and chromatin modification patterns, biasing
