Figure 1. The generation of iPSCs is a multistep process that can be modulated by extracellular cues and reprogramming factor levels.

Known events occurring in early, middle and late phases during the OSKM-mediated reprogramming of mouse embryonic fibroblasts to iPSCs are depicted. During the final emergence of fully reprogrammed iPSCs, the so-called “reprogramming-competent cells” are inhibited by the continued expression of the factors. The reprogramming process can be preferentially trapped in partially reprogrammed states when certain reprogramming factor levels and/or stoichiometry's are employed (top), or can be redirected to a different cell fate, without going through the pluripotent state, by changing culture/growth factor conditions and OSKM expression timing (bottom).