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通过前向编程对人类神经元差异的时间转录调节

Lingling Zhu^1,2, Weiguang Wang³, Jian Zhang¹

¹Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|November 24, 2025

概括

这项研究揭示了不同的人类多能干细胞 (hPSC) 分化方法如何影响神经发生的时间. 关键的基因网络和转录因子控制神经元发育时间,为优化分化策略提供了洞察力.

科学领域:

发展生物学发展生物学
干细胞生物学干细胞生物学
神经科学是一个神经科学.

背景情况:

人类多能干细胞 (hPSCs) 对于研究人类神经生成至关重要.
精确的时间控制hPSC分化成神经元的精确时间控制是不太了解.
对比不同的差异化系统对于理解时间机制至关重要.

研究的目的:

为了比较转录因子 (TF) 诱导的前置编程中的时间控制与hPSC神经发生的双SMAD (DS) 抑制.
识别基因调节网络 (GRNs) 控制分化的时间和细胞命运.
探索GRNs调节如何影响神经发生和神经元成熟时间.

主要方法:

对两个不同的hPSC差异化系统 (TF诱导与DS抑制) 的比较分析.
多原子分析以确定关键基因调节网络 (GRNs).
确定GRNs的扰乱,以评估对神经发生时间的影响.

主要成果:

这两种系统的细胞轨迹不同,导致神经发生的时间不同.
已识别的GRNs具有关键控制细胞命运的决定和分化的时间.
通过NOTCH信号传递,OLIG家族TFs通过NOTCH信号传递促进细胞周期退出,从而影响神经发生的时间.
在两个分化系统中,NEUROD2过度表达加速了神经元的成熟.

结论:

阐明了在hPSCs中差异化时间的基础上的转录机制.
证明GRN和特定的转录因子 (例如,OLIG,NEUROD2) 调节神经发生和成熟时间.
为合理设计控制时间的体外神经元分化策略提供了一个框架.

关键词:

发展时间表的发展时间表.基因调节网络 (GRNs) 是一种基因调节网络.进行多原子分析.神经元分化神经元的分化一步一步的细胞分化.时间过程中单细胞RNA测序.转录因子诱导的前期编程

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