以往的研究證明，O-位N-乙酰葡糖胺（O-linked-N-acetylglucosamine,，O-GlcNAc）修飾廣泛存在于很多蛋白中,，并通過與磷酸化體系競爭絲/蘇氨酸殘基位點(diǎn)來調(diào)節(jié)生物過程，但是在胚胎干細(xì)胞以及細(xì)胞多能性領(lǐng)域,，還沒有與O-GlcNAc有關(guān)的發(fā)現(xiàn),。
本文中，研究人員發(fā)現(xiàn),，O-GlcNAc能夠直接調(diào)節(jié)多能性網(wǎng)絡(luò)的核心元件,。封閉O-GlcNAc作用可阻斷胚胎干細(xì)胞的自我更新過程和從體細(xì)胞誘導(dǎo)成多能干細(xì)胞（iPS）的過程。在胚胎干細(xì)胞中，重要的重編程因子Oct4和Sox2是被O-GlcNAc修飾的,，而在分化過程開始后,，這種修飾會被迅速去除。Oct4 蛋白228位蘇氨酸的O-GlcNAc 修飾能夠調(diào)節(jié)其轉(zhuǎn)錄活性,，同時對于誘導(dǎo)其它多能性相關(guān)因子,，比如Klf2、Klf5,、Nr5a2,、Tbx3和Tcl1的表達(dá)有重要作用。為進(jìn)一步證明O-GlcNAc在重編程中的作用,，研究人員將Oct4突變,，使其228位不能被O-GlcNAc修飾。在突變細(xì)胞中,，胚胎干細(xì)胞的自我更新,，以及體細(xì)胞重編程的效率都受到了影響。研究者據(jù)此得出,，關(guān)鍵轉(zhuǎn)錄因子的O-GlcNAc修飾在維持細(xì)胞多能性網(wǎng)絡(luò)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
