诱导神经元分化的基本转录因子
Congyi Lu1,2, Görkem Garipler2, Chao Dai1,2
1New York Genome Center, New York, NY, USA.
Nature communications
|December 15, 2023
概括
神经原蛋白驱动神经元的分化,但关键的调节者仍然未知. 这项研究确定了重要的转录因子,如ZBTB18,对神经元发育和功能至关重要.
科学领域:
- 神经科学是一个神经科学.
- 发育生物学 发展生物学
- 遗传学 是一个遗传学.
背景情况:
- 神经原蛋白 (NEUROG1,NEUROG2) 是确定神经元身份的关键性前神经转录因子.
- 人类多能干细胞过度表达神经原蛋白,迅速产生皮质类神经元,对疾病建模有价值.
- 驱动神经发生的关键下游调节作用因子仍然不完全理解.
研究的目的:
- 识别介导导向神经元分化的主要转录因子 (TFs).
- 开发一个整合性平台来表征参与人类细胞分化中的TFs.
主要方法:
- 在人类多能干细胞中利用了NEUROG1和NEUROG2的诱导表达.
- 结合表达和染色质可访问性分析,采用合体内CRISPR-Cas9屏幕,针对所有人类TFs.
- 研究了TF功能丧失对神经元分化和形态学的功能影响.
主要成果:
- 确定了几种TFs对于指导神经元差异化至关重要.
- 证明ZBTB18的丧失显著损害了MAP2阳性神经元的产生.
- 在ZBTB18-null细胞中观察到广泛的基因表达改变,细胞骨缺陷和缩的神经元/脊柱.
结论:
- ZBTB18是神经元分化的关键下游TF,影响细胞形态和基因表达.
- 开发的多omics和TFome-wide扰动平台能够快速表征任何人类细胞类型分化所必需的TF.
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