Inherent mitochondrial activity influences specification of the germ line in pluripotent stem cells

Herein we investigated whether inherent differences in mitochondrial activity in mouse pluripotent cells could be used to identify populations with an intrinsic ability to differentiate into primordial germ cells (PGCs). Notably, we determined that stem cells sorted based on differences in mitochondrial membrane activity exhibited altered germline differentiation capacity, with low-mitochondrial membrane potential associated with an increase in PGC-like cells. This specification was not further enhanced by hypoxia. We additionally noted differences between these populations in metabolism, transcriptome, and cell-cycle. These data contribute to a growing body of work demonstrating that pluripotent cells exhibit a large range of mitochondrial activity, which impacts cellular function and differentiation potential. Furthermore, pluripotent cells possess a subpopulation of cells with an improved ability to differentiate into the germ lineage that can be identified based on differences in mitochondrial membrane potential.