Comparative functional genomics identifies unique molecular features of EPSCs.

Extended pluripotent or expanded potential stem cells (EPSCs) possess superior developmental potential to embryonic stem cells (ESCs). However, the molecular underpinning of EPSC maintenance in vitro is not well defined. We comparatively studied transcriptome, chromatin accessibility, active histone modification marks, and relative proteomes of ESCs and the two well-established EPSC lines to probe the molecular foundation underlying EPSC developmental potential. Despite some overlapping transcriptomic and chromatin accessibility features, we defined sets of molecular signatures that distinguish EPSCs from ESCs in transcriptional and translational regulation as well as metabolic control. Interestingly, EPSCs show similar reliance on pluripotency factors Oct4, Sox2, and Nanog for self-renewal as ESCs. Our study provides a rich resource for dissecting the regulatory network that governs the developmental potency of EPSCs and exploring alternative strategies to capture totipotent stem cells in culture.