Comparative functional genomics identifies unique molecular features of EPSCs [ChIP-seq]

Extended pluripotent or expanded potential stem cells (EPSCs) possess the superior developmental potential to embryonic stem cells (ESCs). However, the molecular underpinning of their in vitro maintenance is not well defined. We comparatively studied transcriptome, chromatin accessibility, active histone modification chromatin marks and relative proteomes of ESCs and the two well-established EPSCs to probe the molecular foundation of their unique developmental potential. We found a great overlap in the transcriptomic and chromatin accessibility profiles and reliance on pluripotency factors Oct4, Sox2, and Nanog for self-renewal between ESCs and EPSCs. Importantly, we identified a subset of genomic, transcriptomic, and proteomic signatures that distinguish EPSCs from ESCs in transcriptional and translational regulation as well as epigenetic and metabolic control. We also identified molecular differences between the two well-established EPSCs. Our study provides a rich resource for dissecting the regulatory network underlying the developmental potency of EPSCs and exploring alternative states of totipotency. Overall design: ChIP-seq analysis of mouse extended pluripotent or expanded potential stem cells (EPSCs) and embryonic stem cells (ESCs).