以往的研究证明，O-位N-乙酰葡糖胺（O-linked-N-acetylglucosamine，O-GlcNAc）修饰广泛存在于很多蛋白中，并通过与磷酸化体系竞争丝/苏氨酸残基位点来调节生物过程，但是在胚胎干细胞以及细胞多能性领域，还没有与O-GlcNAc有关的发现。
本文中，研究人员发现，O-GlcNAc能够直接调节多能性网络的核心元件。封闭O-GlcNAc作用可阻断胚胎干细胞的自我更新过程和从体细胞诱导成多能干细胞（iPS）的过程。在胚胎干细胞中，重要的重编程因子Oct4和Sox2是被O-GlcNAc修饰的，而在分化过程开始后，这种修饰会被迅速去除。Oct4 蛋白228位苏氨酸的O-GlcNAc 修饰能够调节其转录活性，同时对于诱导其它多能性相关因子，比如Klf2、Klf5、Nr5a2、Tbx3和Tcl1的表达有重要作用。为进一步证明O-GlcNAc在重编程中的作用，研究人员将Oct4突变，使其228位不能被O-GlcNAc修饰。在突变细胞中，胚胎干细胞的自我更新，以及体细胞重编程的效率都受到了影响。研究者据此得出，关键转录因子的O-GlcNAc修饰在维持细胞多能性网络中有直接作用。（生物谷 Bioon.com ）
doi:10.1016/j.stem.2012.03.001
O-GlcNAc Regulates Pluripotency and Reprogramming by Directly Acting on Core Components of the Pluripotency Network
Hyonchol Jang, Tae Wan Kim, Sungho Yoon, Soo-Youn Choi, Tae-Wook Kang, Seon-Young Kim, Yoo-Wook Kwon, Eun-Jung Cho, Hong-Duk Youn
O-linked-N-acetylglucosamine (O-GlcNAc) has emerged as a critical regulator of diverse cellular processes, but its role in embryonic stem cells (ESCs) and pluripotency has not been investigated. Here we show that O-GlcNAcylation directly regulates core components of the pluripotency network. Blocking O-GlcNAcylation disrupts ESC self-renewal and reprogramming of somatic cells to induced pluripotent stem cells. The core reprogramming factors Oct4 and Sox2 are O-GlcNAcylated in ESCs, but the O-GlcNAc modification is rapidly removed upon differentiation. O-GlcNAc modification of threonine 228 in Oct4 regulates Oct4 transcriptional activity and is important for inducing many pluripotency-related genes, including Klf2, Klf5, Nr5a2, Tbx3, and Tcl1. A T228A point mutation that eliminates this O-GlcNAc modification reduces the capacity of Oct4 to maintain ESC self-renewal and reprogram somatic cells. Overall, our study makes a direct connection between O-GlcNAcylation of key regulatory transcription factors and the activity of the pluripotency network
