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建立大脑器官作为人类特异性大脑进化模型
Alex A Pollen1, Aparna Bhaduri1, Madeline G Andrews1
1Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA, USA; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, UCSF, San Francisco, CA, USA.
Cell
|February 9, 2019
概括
人类大脑的发展涉及独特的分子路径. 研究人员使用脑器官识别基因和信号通路, 比如PI3K-AKT-mTOR,
科学领域:
- 神经科学
- 发育生物学
- 进化生物学
背景情况:
- 直接比较人类和非人类灵长类的大脑对于理解人类大脑的专业化至关重要.
- 在关键的新皮层发育阶段, 黑猩猩的大脑组织是不可用的, 阻碍了早期大脑大小差异的研究.
研究的目的:
- 确定皮层发育的特定分子特征.
- 建立一个分析分子变化的平台,
主要方法:
- 来自黑猩猩的多能干细胞的脑器官.
- 人类和黑猩猩的基因表达和皮的比较.
- 分析PI3K-AKT-mTOR信号通路在人类的辐射质.
主要成果:
- 尽管有代谢差异,但有机体模型保留了关键的基因调节网络.
- 在人类与黑猩猩有机体和皮层中鉴定了261个差异表达的基因,并为最近的基因复制增添了丰富性.
- 观察到PI3K- AKT- mTOR通路在人体辐射质细胞中的激活增加,这取决于人体特定的INSR和ITGB8受体.
结论:
- 人类大脑器官为研究人类特异性大脑发育提供了可行的模型.
- 最近的基因重复和PI3K-AKT-mTOR通路,由INSR和ITGB8调节,与人类皮层进化有关.
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