O-GlcNAc is required for the survival of primed pluripotent stem cells and their reversion to the naïve state

Abstract

“Naïve” mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. “Primed” mouse epiblast stem cells (EpiSCs) are also pluripotent but are derived from post-implantation embryos. ESC-derived EpiSCs (ESD-EpiSCs) are “primed” pluripotent stem cells and can revert to naïve reverted ESCs (rESCs). O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a posttranslational modification in the cytoplasm and nucleus. O-GlcNAc is transferred to serine and threonine residues of proteins by O-GlcNAc transferase (Ogt) and removed from them by O-GlcNAcase (Oga). In naïve ESCs, O-GlcNAc contributes to maintain the undifferentiated state. In the transition from naïve state to primed state, Ogt maintains cell survival, whereas Oga has no function. However, the function of O-GlcNAc in primed ESD-EpiSCs and during the reversion from the primed state to naïve rESCs remains unclear. Here, we show that Ogt is required for the survival of primed ESD-EpiSCs. The expression of cytosolic Oga was significantly increased during induction from naïve ESCs to primed ESD-EpiSCs. Furthermore, both Ogt and Oga were required for the reversion from primed ESD-EpiSCs to naïve rESCs. These findings indicate that O-GlcNAcylation plays an important role in the survival of primed ESD-EpiSCs and in their reversion to naïve rESCs.