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用L-MYC-永生化的人类神经干细胞衍生器官在体外模型中进行大脑发育

Alejandra Velazquez Ojeda¹, Dina Awabdeh¹, Blake Brewster¹

¹Department of Stem Cell Biology & Regenerative Medicine, Beckman Research Institute and National Medical Center, City of Hope, Duarte CA 91010.

bioRxiv : the preprint server for biology

|February 24, 2025

概括

这项研究介绍了一种新型的人类大脑器官平台,使用L-MYC永生的神经干细胞. 这些器官模仿人类大脑发育和基因表达,为研究和治疗提供了更好的模型.

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:

人类大脑有机体为研究发育和疾病提供了先进的"活体模型",超越了以前的"体外"系统和动物模型的局限性.
人类组织和不完美的动物模型的有限访问历史上阻碍了人类大脑发育研究.

研究的目的:

通过使用L-MYC永生化的人类胎儿神经干细胞 (LMNSC01) 呈现一种基于器官的新型研究平台.
为了评估这些有机体的发育模式和基因表达 *in vitro* 与正常人类大脑发育相比.

主要方法:

使用L-MYC永生化的人类胎儿神经干细胞 (LMNSC01),培养在4%的生理氧气环境中.
通过免疫光和NanoString基因表达造型,在120天内*体外*可视化发育过程.
通过使用*Singscore*方法,从数量上将有机基因表达与BrainSpan数据库进行了比较.

主要成果:

LMNSC01有机体表现出类似于人类皮层发育的神经元,星细胞和寡细胞标记物的发育模式.
在与亡,神经元细胞骨架,神经传递和新陈代谢相关的途径中观察到可比的基因表达模式.
突出平台的一致性,使用永生的人类神经干细胞和生理氧气条件.

结论:

LMNSC01大脑器官平台为研究人类大脑发育 *ex vivo* 提供了一种一致且可靠的模型.
该平台显示了与正常皮质发育相比较的有利基因表达特征,促进了治疗策略的制定.

关键词:

人类神经干细胞是神经干细胞.细胞 LMNSC01 的细胞.从NSC衍生的有机物.神经谱系分化分化神经谱系分化

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