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Reprogramming somatic cells into a pluripotent state involves the overexpression of transcription factors leading to a series of changes that end in the formation of induced pluripotent stem cells (iPSCs). These iPSCs have a wide range of potential uses from drug testing and in vitro disease modelling to personalized cell therapies for patients. While viral methods for reprogramming factor delivery have been traditionally preferred due to their high efficiency, it is now possible to generate iPSCs using nonviral methods at similar efficiencies. We developed a robust reprogramming strategy that combines episomal plasmids and the use of commercially available animal free reagents that can be easily adapted for the GMP manufacture of clinical grade cells.

In mammals, one of the two X chromosomes in female cells is transcriptionally silenced for dosage compensation between the sexes. Chromosome-wide silencing is initiated by the non-coding Xist RNA that accumulates within the inactive X chromosome territory and triggers gene repression and chromatin modifications. Epigenetic changes of the inactive X chromosome in a developmentally regulated manner result in stable gene repression in female somatic cells. X inactivation is a model for understanding the formation of facultative heterochromatin in mammalian development and represents a paradigm for RNA mediated regulation of gene expression. In this review, we summarize the present knowledge of the mechanism of chromosome-wide silencing and give an outlook on future directions.