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Cell Stem Cell:Oct4糖基化修饰调节细胞多能性

来源:生物谷 2012-06-04 21:20

 

O-连接-N-乙酰氨基葡萄糖(O-GlcNAc)是许多细胞功能的关键调控因子,但是它在胚胎干细胞(ESCs)及多能性中的作用尚不清楚。5月17日Cell Stem Cell杂志在线发表了Hyonchol Jang等人的研究论文,报道称O-GlcNAc化修饰可直接调节多能性细胞信号网络的关键成分。

 

研究显示,阻断O-GlcNAc化修饰将破坏ESC的自我更新并使体细胞不能被诱导为多能干细胞。在ESCs中,核心重编程因子Oct4 和Sox2是O-GlcNAc化的,但这种修饰随着分化的进行而被迅速去除了。Oct4中228位苏氨酸的O-GlcNAc化调节着Oct4的转录活性,对调节许多多能性相关基因,如Klf2, Klf5, Nr5a2, Tbx3, 和 Tcl1,具有重要作用。Oct4的点突变T228A可破坏O-GlcNAc化修饰,进而降低Oct4保持ESC自我更新和重新编程体细胞的能力。

 

总之,该研究证实了O-GlcNAc化修饰与细胞多能性调控网络的关键转录因子是密切相关的。(生物谷bioon.com)

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.

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