Fig. 1

a In vitro differentiation model developed for this study. Embryonic Stem Cells (ESC) are induced to form Epiblast-Like Aggregates (ELA) which are similar to the post-implantation epiblast in vivo. ESC-to-ELA transition mimics early differentiation stages of cells from the inner cell mass of the blastocyst that give rise to epiblast cells after implantation. Further differentiation of ELA-to-neural progenitors can be achieved in vitro, and serve as a model to study later stages of differentiation. b RISC-mediated inhibition of translation of chromatin regulators during early priming. Naïve pluripotent stem cells (left chart) express Nanog, Klf4 and Rex1 genes. Chromatin remodelers such as DNA methyltransferases (DNMT), Lysine demethylases (KDM) and members of the SWItch/Sucrose Non-Fermentable complex (SWI/SNF) are expressed (mRNA depicted as wavy lines) both in naïve (left chart) and primed cells (right chart), but in naïve pluripotency they are translationally inhibited (ribosomes depicted in grey) through the RNA-induced silencing complex (RISC) and naïve specific miRNAs. Once cells become primed, naïve specific miRNAs are downregulated, allowing for the release from the RISC complex of the mRNAs coding for these chromatin regulators. Increased translation of DNMT, KDM and SWI/SNF proteins leads to the shutdown of ground pluripotency transcriptional programs, including genes such as Nanog, Klf4 and Rex1