Fig. 8

Two-layer model of epigenetic control of pluripotency. A marked release from RISC characterizes the ES–ELA transition (priming), whereas transcriptional regulation occurs preferentially at the ELA–NPC transition (neuralization). Our data suggest a causal link between the two phenomena as the pool of de-repressed genes contains distinct chromatin regulators which could overcome the epigenetic barrier between the primed state and ground-state pluripotency. Thus, ground-state miRNAs, which are down-regulated during priming, could shield naïve pluripotent cells from the epigenetic transition required for the onset of embryonic differentiation programs