Epigenetic Regulation of Pluripotency and Differentiation

Abstract

The precise, temporal order of gene expression during development is critical to ensure proper lineage commitment, cell fate determination, and ultimately, organogenesis. Epigenetic regulation of chromatin structure is fundamental to the activation or repression of genes during embryonic development. In recent years there has been an explosion of research relating to various modes of epigenetic regulation such as DNA methylation, posttranslational histone tail modifications, non-coding RNA control of chromatin structure, and nucleosome remodeling. Technological advances in genome wide epigenetic profiling and pluripotent stem cell (PSC) differentiation have been primary drivers for elucidating the epigenetic control of cellular identity during development and nuclear reprogramming. Not only do epigenetic mechanisms regulate transcriptional states in a cell type-specific manner but they also establish higher-order genomic topology and nuclear architecture. Here, we review the epigenetic control of pluripotency and changes associated with PSC differentiation. We focus on DNA methylation and demethylation, and common histone tail modifications. Finally, we briefly discuss epigenetic heterogeneity among PSC lines and the influence of epigenetic patterns on genome topology.

Effects of C-Reactive Protein on the Cardiac Differentiation of Mouse Embryonic Stem Cells

“…5-Aza was used in our study, as in many other previously published literatures. [21][22][23][24] 5′-Aza is an inhibitor of DNA methylation, and is critical in the induction of new developmental pathways in cultured cells since cell differentiation involves stable and heritable changes, presumably of an epigenetic nature. 24) Of note, the cardiomyocytes differentiated from ES cells for 16 d were used for fur- ther electrophysiological examinations (Figs.…”

Epigenetic modification in congenital heart diseases by using stem cell technologies

“…These results suggest that we could treat some congenital heart diseases by using chemical reagents. However, for iPS cells, we have to take the issue of epigenetic memory into consideration, namely, the retention of the epigenetic signature of somatic cells from which iPS cells originated [59,60] . Numerous studies have reported that iPS cells retained epigenetic memory and that they tended to differentiate into their original cell types [61,65,66] .…”

“…However, iPS cells have a special feature: epigenetic memory. Epigenetic memory is the phenomenon by which iPS cells still have the epigenetic signature of the donor somatic cells, even after reprogramming [59,60] . This epigenetic memory is caused by incomplete silencing of the donor cell-specific gene expression patterns; the majority of this is attributed to DNA methylation [61,62] because histone modifications were shown to be similar between iPS cells and ES cells [63,64] .…”

Advances in Reprogramming-Based Study of Neurologic Disorders

“…In addition, cellular reprogramming involves genomewide epigenetic changes that are not typical of normal embryonic development, which may result in imperfect, aberrant, or incomplete resetting of the epigenetic landscape of the donor cell [114,115]. Recent improvements in reprogramming protocols have repeatedly shown that chemical manipulations that increase the accessibility of the chromatin to the cell's transcriptional machinery, can contribute to improved reprogramming efficiency [116][117][118][119].…”