通过直接转录激活Sox2,Ars2维持神经干细胞的身份
Celia Andreu-Agullo1, Thomas Maurin, Craig B Thompson
1Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, New York 10065, USA. andreuac@mskcc.org
Nature
|December 27, 2011
概括
指蛋白Ars2 (酸盐抗性蛋白2) 对于神经干细胞 (NSC) 的自我更新和认同至关重要. Ars2直接激活Sox2的表达,保持NSCs的多能原始状态.
科学领域:
- 神经科学是一个神经科学.
- 干细胞生物学 干细胞生物学
- 分子生物学分子生物学
背景情况:
- 神经干细胞 (NSC) 具有自我更新和神经发生能力,但控制它们的转录网络仍然不清楚.
- Ars2 (酸盐抗性蛋白-2) 是一种指蛋白,在微RNA生物发生过程中具有已知的作用.
- 在成人神经干细胞身份和自我更新中Ars2的功能尚不清楚.
研究的目的:
- 研究Ars2在成人神经干细胞自我更新和身份中的作用.
- 确定Ars2调节神经干细胞功能的分子机制.
主要方法:
- 在成人腹腔下区域 (SVZ) 的状纤维酸性蛋白质表达细胞中选择性的Ars2淘汰.
- 产生hGFAP-cre::Ars2(fl/fl) 条件淘汰小鼠. 有条件的淘汰小鼠.
- 外体检测测试验以评估NSC自我更新和神经生成能力.
- 染色体免疫沉和凝转移分析以确定Ars2结合部位.
- 在Ars2-缺乏的NSC中评估Sox2表达和功能.
主要成果:
- 在成年SVZNS中,Ars2的淘汰削弱了NSC的数量和神经性能力.
- 条件淘汰Ars2在小鼠中重复并加剧了这些表型.
- Ars2以RNA独立的方式直接与Sox2基因的特定增强器区域结合.
- Ars2积极调节Sox2的表达,这对于NSC自我更新和多效能至关重要.
- Ars2促进NSC自我更新,独立于其在microRNA生物发生中的已知作用.
结论:
- Ars2是一种新型的转录因子,对于维持神经干细胞的多能原始体状态至关重要.
- Ars2直接激活Sox2的表达,从而控制NSC的身份和自我更新.
- 这些发现揭示了神经干细胞维护和神经发生的新调节机制.
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