Stem Cell Epigenetics: Insights from Studies on Embryonic, Induced Pluripotent, and Germline Stem Cells

Abstract

Embryonic stem cells and induced pluripotent stem cells (iPSCs) exhibit similar and unique epigenetic features that endow them with pluripotency. Pluripotent cells have highly plastic genomes that display open chromatin that is abundantly marked by active histone modifications, making it poised for differentiation cues. This is in contrast to lineage-committed cells, which have condensed heterochromatin and large blocks of repressive chromatin domains. A recent study of spermatogonial stem cells showed dynamic epigenetic changes occur during differentiation, suggesting that, in both embryonic- and adult-type stem cells, global epigenetic regulation serves as a barrier between stem and differentiated cells. Reprogramming requires that this epigenetic barrier be overcome for faithful gene expression patterns to be established. Evidence suggests that incomplete epigenetic reprogramming is common in iPSCs, highlighting potentially serious problems for clinical applications. Here, we review insights and major progress obtained from in vitro stem cell studies, as well as in vivo characterization of stem cells in the germline.