MLL1: the thin red line divides naïve and primed pluripotency

From mouse pre-implantation and early post-implantation embryos, stem cells at different pluripotent states can be captured in in vitro culture. For example, naïve embryonic stem cells (ESC) are derived from inner cell mass (ICM) of the blastocyst, while primed epiblast stem cells (EpiSC) are captured from the post-implantation embryo epiblast. Though both ESCs and EpiSCs are pluripotent stem cells, they have distinct characters in terms of pluripotent gene expression profile, epigenetic status, metabolic pathways, growth factor requirement, and in female, the X chromosome inactivation status (1). On the other hand, these two pluripotent states are interchangeable, once switching the culture condition of ESCs to that for EpiSCs, naïve ESCs convert to EpiSCs. The efficiency of converting EpiSCs to ESCs, however, is much low, which usually requires over-expressing pluripotency-associated genes such as Nanog, Klf4, Esrrb, Tfcp2l1 and Nr5a2 (2-6). Similar to somatic cell reprogramming to induced pluripotent stem cells, converting EpiSCs to ESCs is an epigenome-resetting process. Characterizing these epigenetic barriers represents an important approach to further improve reprogramming efficiency (7).