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在METTL3-依赖的N6-甲基氨酸修饰程序的人类神经原始细胞的增殖

Yuan Zhao^1,2, Jianguo Li^1,2, Yilin Lian^1,2

¹Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Maternal Fetal Medicine, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.

International journal of molecular sciences

|November 14, 2023

概括

甲基转移酶类3 (METTL3) 通过通过N6-甲基氨酸修饰来调节SLIT2表达,对人类神经前代细胞的增殖至关重要. 通过降低SLIT2mRNA水平,METTL3缺乏会损害增殖.

科学领域:

表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
发育神经科学的发展神经科学.
在RNA生物学,RNA生物学.

背景情况:

METTL3是N6-甲基氨酸 (m6A) 修饰的一个关键甲基转移酶.
m6A在哺乳动物中枢神经系统 (CNS) 发育中起调节作用.
人体中枢神经系统发育中的特定表观遗传机制尚未完全理解.

研究的目的:

研究METTL3在人类神经原生细胞 (hNPC) 形成,分化和增殖中的作用.
阐明人类中枢神经系统发育中的METTL3功能背后的表观遗传机制.

主要方法:

产生了小分子辅助关闭 (SMASh) 标记的人类胚胎干细胞 (hESC) 线来降低METTL3水平.
评估了hNPC的形成和神经元的分化.
量化的hNPC增殖和SLIT2表达.
在SLIT2 mRNA中分析了m6A丰富.

主要成果:

对于hNPC的形成或神经元的分化,METTL3不是必不可少的.
METTL3缺乏抑制了hNPC的扩散.
这种抑制与减少SLIT2表达有关.
METTL3降解降低了SLIT2mRNA中的m6A丰富,导致表达较低.

结论:

METTL3对于hNPC的扩散至关重要,而不是初始形成或分化.
SLIT2是hNPCs中METTL3的一个新功能标.
这项研究增强了对hNPC扩散中的m6A依赖机制的理解.

关键词:

在METTL3中,METTL3是METTL3的第一个类型.在SLIT2中,我们使用的是SLIT2.这就是为什么hESCs.在hNPCs中,m6A 一个很好的.神经分化的神经分化.它们的扩散和扩散.

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