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在动物中移植的人类皮质器官的宿主电路参与

Kevin W Kelley^1,2, Omer Revah^1,2, Felicity Gore^1,3

¹Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.

Nature protocols

|July 29, 2024

概括

将人类皮层有机体 (hCOs) 移植到老鼠大脑中,可以实现体内成熟和功能电路集成. 这种方法可以研究人类的神经发育和疾病在一个活体系统.

科学领域:

神经科学是一个神经科学.
发展生物学发展生物学
干细胞研究干细胞研究

背景情况:

在实验室中,人类神经器官缺乏成熟的必要微环境.
移植到动物宿主中可以改善有机体发育和电路集成.

研究的目的:

描述一种将人类干细胞衍生的皮质器官 (hCOs) 移植到新生小鼠宿主中的方法.
在体内证明移植的人类神经组织的功能整合和特征.

主要方法:

人类诱导的多能干细胞分化为hCOs (30-60天).
在新生小鼠的体感皮层进行手术移植 (约0.5-1小时的手术).
在体内监测 (成像,电生理学),光遗传行为范式和体外表征 (形态学,转录学).

主要成果:

成功移植和hCOs在老鼠宿主中存活了数百天.
在体内证明了神经电路功能和与主机电路的功能集成.
能够对人类神经元特征进行详细的ex vivo分析.

结论:

移植到新生儿宿主中为hCO成熟和集成提供了一个发育适当的平台.
这种方法促进了人类神经发育,进化和患者特异性的细胞表型的研究.
能够研究以前无法获得的发育阶段和人类大脑功能和疾病的机制.

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