Following implantation, mouse epiblast cells transit from a nave to a primed state in which they are competent for both somatic and primordial germ cell (PGC) specification. Using mouse embryonic stem cells (mESC) as an in vitro model to study the transcriptional regulatory principles orchestrating peri-implantation development, here we show that the transcription factor Foxd3 is necessary for the exit from nave pluripotency and the progression to a primed pluripotent state. During this transition, Foxd3 acts as a repressor that dismantles a significant fraction of the nave pluripotency expression program through the decommissioning of active enhancers associated with key nave pluripotency and early germline genes. Subsequently, Foxd3 needs to be silenced in primed pluripotent cells to allow the reactivation of relevant genes required for proper PGC specification. Our findings uncover a wave of activation-deactivation of Foxd3 as a crucial step for the exit from nave pluripotency and subsequent PGC specification. SOURCE: Alvaro Rada-IglesiasDevelopmental genomics Center for Molecular Medicine Cologne

Pluto Bioinformatics

GSE70546: Foxd3 promotes the exit from nave pluripotency and prevents germline specification through enhancer decommissioning [RNA-Seq]