Deciphering the mechanisms of epigenetic reprogramming provides fundamental insights into cell fate decisions, which in turn reveal strategies to make the reprogramming process increasingly efficient. Here we review recent advances in epigenetic reprogramming to pluripotency with a focus on the principal molecular regulators. We examine the trajectories connecting somatic and pluripotent cells, genetic and chemical methodologies for inducing pluripotency, the role of endogenous master transcription factors in establishing the pluripotent state, and functional interactions between reprogramming factors and epigenetic regulators. Defining the crosstalk among the diverse molecular actors implicated in cellular reprogramming presents a major challenge for future inquiry.
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