在成年神经干细胞中,分化的开始是通过转录控制的
Avni Baser1,2, Maxim Skabkin1, Susanne Kleber1
1Molecular Neurobiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Nature
|February 1, 2019
概括
干细胞通过调节蛋白质合成来控制分化. 随着干细胞成熟成为神经元, 翻译变得更加可控,
科学领域:
- 分子生物学
- 发育生物学
- 干细胞生物学
背景情况:
- 静止干细胞保持低蛋白质合成的功能.
- 神经元将mRNA存储在静态状态中以快速响应.
- 转录后调节在干细胞分化中的作用尚不清楚.
研究的目的:
- 研究转录后调控如何控制干细胞分化.
- 确定干细胞成熟到神经元时蛋白质合成的变化.
- 确定将细胞周期输出与干结合的机制.
主要方法:
- 使用RiboTag小鼠模型来检查个别的转录翻译.
- 在体内干细胞分化过程中分析了蛋白质合成的变化.
- 评估了mTORC1活动在调节翻译中的作用.
主要成果:
- 干细胞转换最初是无差别的,但在分化过程中会受到调节.
- 神经性后代的产生涉及干细胞因子 (SOX2,PAX6) 和转化机制组件的转化抑制.
- 减少的mTORC1活性选择性地阻断了富含胺基因的特定mRNA的翻译.
- 确定了一种机制,将细胞周期的退出与干细胞因子的转录后抑制联系起来.
结论:
- 在干细胞分化成神经元过程中,蛋白质合成受到动态调节.
- 干细胞身份因子的转录后抑制促进了干细胞的退出.
- 这项研究揭示了干细胞命运的新控制机制.
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