灵长类细胞融合解开神经发育中的基因调节分歧
Rachel M Agoglia1, Danqiong Sun2, Fikri Birey3
1Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Nature
|March 18, 2021
概括
科学家将人类和黑猩猩的干细胞结合起来, 制造出混合器官, 揭示了大脑发育中的关键遗传差异, 并确定了与神经精神疾病相关的人类特异基因.
科学领域:
- 进化生物学
- 发展神经科学
- 遗传学
背景情况:
- 由于对灵长类组织的访问有限, 研究人类进化是具有挑战性的.
- 使用诱导多能干细胞进行的体外比较研究提供了对物种特征的洞察力.
- 大脑器官对于研究灵长类神经发育有价值,但跨物种比较面临挑战.
研究的目的:
- 开发一种用于研究灵长类大脑皮层发育的新平台.
- 克服跨物种有机体比较的局限性,例如发育时间和差异化变异性.
- 调查基因表达的分歧,并确定人类特有的分子基础.
主要方法:
- 通过将人类和黑猩猩诱导的多能干细胞融合,生成四体混合干细胞.
- 将混合干细胞分化为神经器官,进行比较分析.
- 在细胞类型和发育阶段之间分析cis和trans作用的基因表达分歧.
主要成果:
- 混合器官提供了一个可控的系统来剖析人类和黑猩猩神经发育之间的基因表达差异.
- 在与天体细胞相关的基因上发现了选择的特征.
- 观察到人体体静止素受体2基因 (SSTR2) 的升级,对其调节产生人体特异性反应.
结论:
- 四状混合干细胞平台可以详细研究神经发育中的特定物种基因调节.
- 这些发现突显了与星细胞相关的基因和SSTR2在人类进化分歧中的作用.
- 这种方法有可能阐明人类进化和相关疾病的分子基础.
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