title: 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.
authors.affiliation: Department of Bioinformatics, Graduate School of Engineering, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo 192-8577, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Miura
authors.affiliation: Department of Bioinformatics, Graduate School of Engineering, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo 192-8577, Japan. Electronic address: shoko@soka.ac.jp.
authors.forename: Shoko
authors.initials: S
authors.lastname: Nishihara
mesh_terms: D000215:Acylation / Q000502:physiology; D000818:Animals; D054337:Cell Dedifferentiation / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D051379:Mice; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology*; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism*
chemical_list: D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases
keywords: ESC-derived epiblast stem cells; Embryonic stem cells; O-GlcNAc; O-GlcNAc transferase; O-GlcNAcase