主要-自-Nrf2 (PAN) 轴激活使人类胚胎干细胞成为神经外皮的命运
Jiwon Jang1, Yidi Wang1, Matthew A Lalli1
1Department of Molecular Cellular Developmental Biology, Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Cell
|March 30, 2016
概括
人类胚胎干细胞 (hESCs) 通过主-自-Nrf2 (PAN) 轴分化为神经内皮 (NE). 这种途径调节细胞循环和多能基因表达,指导早期的神经发育.
科学领域:
- 干细胞生物学
- 发育生物学
- 细胞信号传输
背景情况:
- 人类胚胎干细胞 (hESC) 分化为中皮层 (ME) 或神经皮层 (NE).
- 早期的血统规范涉及细胞周期的变化和纤维化模式.
研究的目的:
- 确定控制hESCs初始神经外皮 (NE) 命运决定的分子机制.
- 阐明初级乳毛,自和Nrf2在指导hESC分化中的作用.
主要方法:
- 在定义条件下诱导hESC分化.
- 分析纤维化模式,细胞周期进展 (G1延长) 和基因表达 (OCT4,NANOG,Nrf2).
- 研究自诱导及其对Nrf2和多能性因子的影响.
主要成果:
- 在24小时内出现了分离的纤维化模式,先于神经标志物表达.
- 在NE前体中增加的纤维化诱导了自,在第二天激活了Nrf2.
- 无活性化缓解了OCT4和NANOG的抑制,促进了NE的衍生.
- 在患者诱导的多能干细胞 (iPSC) 中,Nrf2抑制挽救了神经发生.
- 只有在这些上游事件发生后,神经前体标记才被表达出来.
结论:
- 一个与细胞循环进展相关的新型初级-自-Nrf2 (PAN) 控制轴,将hESC分化指向神经外皮 (NE) 命运.
- 这一轴在正规神经前体标记表达的上游作用.
- PAN轴为早期神经发育提供了关键的调节机制,可能是改善iPSC神经发生的目标.
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