Reprogramming cell fate to pluripotency: the decision-making signalling pathways.

Pluripotency can be defined as the ability of individual cells to initiate all of the lineages of the mature organism in response to signals from the environment. It has long been assumed that during development, pluripotency is progressively and irreversibly lost through a mechanism that requires strict coordination of the signalling pathways involved in cell proliferation, differentiation and migration. However, recent breakthroughs have highlighted evidence that terminally differentiated cells can be reprogrammed into pluripotent stem cells, prompting a re-evaluation of the reversibility of cell differentiation. Generations of pluripotent cells can arise from somatic cells following ectopic expression of specific transcription factors; however, these factors might well not be the unique essential reprogramming factors. Furthermore, they can be the end-point targets of signalling pathways. Indeed, recent evidence shows that modulation of the Wnt/beta-catenin, MAPK/ERK, TGF-beta or PI3K/Akt signalling pathways strikingly enhances somatic-cell reprogramming. Nevertheless, we still know relatively little about the underlying mechanisms by which somatic cells de-differentiate to pluripotency. In this review, we provide an overview of the signalling pathways promoting the re-acquisition and maintenance of pluripotency and we discuss the possible mechanisms underlying nuclear reprogramming.