In this study, we explored epigenetic and transcriptional variation in the most comprehensive collection of hPSC and somatic samples to date. Using a combination of genome-wide DNA methylation and mRNA expression data, we identified unique epigenetic and transcriptional properties of the pluripotent state. Most distinctive among these characteristics are prevalent, but not uniform, losses of imprinting and XCI and consistent hypermethylation of somatic cell-type-specific genes in hPSCs. We observed the acquisition of the appropriate cell-type-specific DNA methylation marks during differentiation of hPSCs, despite persistence of aberrant imprinting and XCI. The scope and resolution of our study has allowed us to address many inconsistencies in the literature, which arose from the inclusion of limited numbers of cell lines and/or sparse coverage of the genome.
