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Somatic cell reprogramming control: Signaling pathway modulation versus transcription factor activities

In all cells of the body, differentiation from zygotes has been considered a unidirectional route. Recently, however, it has become clear that the reverse path is indeed possible, in the reprogramming of somatic nuclei, i.e. the de-differentiation of somatic cells into pluripotent stem-like cells. Breakthrough discoveries have shown that over-expression of a combination of transcription factors can allow a somatic cell nucleus to be reprogrammed. Furthermore, very recently it has been shown that modulation of the Wnt/β-catenin, MAPK/ERK and PI3K/Akt signalling pathways strikingly enhances reprogramming efficiency. Despite these important findings, the molecular mechanisms driving reprogramming are still largely unknown, and moreover, it is not clear if and how these different routes for the triggering of somatic cell reprogramming converge, i.e. the over-expression of transcription factors and the modulation of signalling pathways. Here, we consider these different reprogramming routes and discuss how they can cooperate in parallel to enhance somatic cell reprogramming.