Redox and epigenetics in human pluripotent stem cells differentiation.

Since their discovery, induced pluripotent stem cells (iPSC) had generated considerable interest in the scientific community for the great potential in regenerative medicine, disease modeling and cell-based therapeutic approached, due to their unique characteristics of self-renewal and pluripotency. Technological advances in iPSC genome wide epigenetic profiling, led to the elucidation of the epigenetic control of cellular identity during nuclear reprogramming. Moreover, iPSC physiology and metabolism are tightly regulated by oxidation-reduction events that mainly occur during respiratory chain. In theory, iPSC-derived differentiated cells would be ideal for stem cell transplantation as autologous cells from donors, as the risks of rejection are minimal. However, iPSC experience high oxidative stress that in turn confers high risk of increased genomic instability, which is most often linked to DNA repair deficiencies. Genomic instability has to be assessed before that iPSC can be used in therapeutic designs. This review will particularly focus on the links between redox balance and epigenetic modifications - in particular based on the histone variant macroH2A1 - that determine DNA damage response in iPSC and derived differentiated cells, and that might be exploited to decrease the teratogenic potential upon iPSC transplantation.