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通过单细胞转录组合模式屏幕编程人类神经元亚型

Hsiu-Chuan Lin¹, Jasper Janssens¹, Benedikt Eisinger¹

¹Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.

Science (New York, N.Y.)

|July 10, 2025

概括

研究人员通过将发育信号调节与转录因子 (TF) 过度表达相结合,扩大了体外产生的人类神经元亚型的多样性. 这种方法成功地模拟了多种神经元亚型,为疾病建模和再生医学提供了新的途径.

科学领域:

神经科学
干细胞生物学
发育生物学

背景情况:

转录因子 (TF) 的过度表达是人类神经元差异化和疾病的关键方法.
可以在体外生成的神经元亚型的全谱在很大程度上仍未被探索.

研究的目的:

研究从多能干细胞编程的神经元亚型的多样性.
探索发育信号通路和TF过度表达的组合,以产生多种神经元亚型.

主要方法:

调节发育信号通路与TF过度表达.
对480个形态原信号调制和TF诱导组合进行选.
对超过70万个细胞进行多重复合的单细胞转录组分析.

主要成果:

人类激发性和抑制性神经元的识别.
神经管的发育轴沿着神经子类型的模式.
通过访问原始组织相关的基因调节网络,预模式神经元增强了神经元多样性.

结论:

将发育信号调制与TF过度表达相结合,显著扩大了可编程神经元亚型的多样性.
这一策略使人类神经元子类型的生成能够反映体内发现的子类型.
这些发现为产生多样化的人类细胞亚型和研究信号在神经元命运决定中的作用提供了框架.

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