O-連接-N-乙酰氨基葡萄糖（O-GlcNAc）是許多細胞功能的關鍵調控因子,，但是它在胚胎干細胞（ESCs）及多能性中的作用尚不清楚,。5月17日Cell Stem Cell雜志在線發(fā)表了Hyonchol Jang等人的研究論文，報道稱O-GlcNAc化修飾可直接調節(jié)多能性細胞信號網(wǎng)絡的關鍵成分,。
研究顯示,，阻斷O-GlcNAc化修飾將破壞ESC的自我更新并使體細胞不能被誘導為多能干細胞。在ESCs中,，核心重編程因子Oct4 和Sox2是O-GlcNAc化的,，但這種修飾隨著分化的進行而被迅速去除了。Oct4中228位蘇氨酸的O-GlcNAc化調節(jié)著Oct4的轉錄活性,，對調節(jié)許多多能性相關基因,，如Klf2, Klf5, Nr5a2, Tbx3, 和 Tcl1，具有重要作用,。Oct4的點突變T228A可破壞O-GlcNAc化修飾，進而降低Oct4保持ESC自我更新和重新編程體細胞的能力,。
總之,，該研究證實了O-GlcNAc化修飾與細胞多能性調控網(wǎng)絡的關鍵轉錄因子是密切相關的。（生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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O-GlcNAc Regulates Pluripotency and Reprogramming by Directly Acting on Core Components of the Pluripotency Network
Hyonchol Jang, Tae Wan Kim, Sungho Yoon,et al
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
