Source cell-type epigenetic memory persists in induced pluripotent cells but is lost in subsequently derived germline cells

Past studies have shown that retention of source cell-type epigenetic memory may mitigate the potential for induced pluripotent stem cells (iPSCs) to fully achieve transitions in cell fate in vitro. While this may not preclude the use of iPSC-derived somatic cell types for therapeutic applications, it becomes a major concern impacting the potential use of iPSC-derived germline cell types for reproductive applications. Importantly, the transition from a source somatic cell type to iPSCs and then on to germ-cell like cells (GCLCs) recapitulates, at least in part, two major epigenetic reprogramming events that normally occur during development in vivo - embryonic reprogramming in the epiblast and germline reprogramming in primordial germ cells (PGCs). We examined the extent of epigenetic and transcriptomic memory persisting first during the transition from differentiated source somatic or germ cell types to iPSCs, and then during the transition from iPSCs to PGC-like cells (PGCLCs).