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长非编码RNA nHOTAIRM1 对于iPSC衍生的脊柱运动神经元的分化和活动是必要的

Paolo Tollis^1,2, Erika Vitiello^1,3, Francesco Migliaccio^4,5

¹Department of Biology and Biotechnologies "C. Darwin", Sapienza University of Rome, Rome, Italy.

Cell death & disease

|November 14, 2023

概括

长非编码RNAHOTAIRM1 (nHOTAIRM1) 对于脊柱运动神经元 (MN) 发育至关重要. 它促进了MN命运,增强了神经元的增长,并确保了适当的突触功能,突出了它在神经元生物学中的作用.

科学领域:

神经科学是一个神经科学.
分子生物学分子生物学
发展生物学发展生物学

背景情况:

哺乳动物的神经系统包括多样化的细胞,复杂的连接,由蛋白质和RNAs调节.
运动神经元 (MN) 控制基本功能,其发展历史上归因于蛋白质因素.
长非编码RNAs (lncRNAs) 越来越多地被认为是中枢神经系统 (CNS) 中的关键调节者.

研究的目的:

为了研究HOTAIRM1 (nHOTAIRM1) 神经元异型的新功能,这是一种特定于脊髓的lncRNA.
确定nHOTAIRM1在脊柱运动神经元 (spMN) 区分和功能中的作用.
阐明nHOTAIRM1在spMN中的监管活动的机制基础.

主要方法:

利用一个模型系统来区分脊髓运动神经元.
由人类诱导的多能干细胞 (iPSC) 衍生的 spMN 缺乏 nHOTAIRM1.1.
分析了神经元的生长,细胞命运决定,基因表达和蛋白质相互作用.

主要成果:

nHOTAIRM1充当前运动神经元因素,影响MNs和内神经元之间的细胞命运决定.
在人类iPSC衍生的spMNs中缺少nHOTAIRM1导致神经元外生受损 (分支和结节减少).
nHOTAIRM1缺乏导致突触连接和神经传递至关重要的基因表达受损.

结论:

该lncRNA nHOTAIRM1对于指定运动神经元身份至关重要.
nHOTAIRM1在转基因后运动神经元的形态发育和突触活动中发挥着关键作用.
nHOTAIRM1 作为细胞质中的转录后调节剂,影响运动神经元生物学.

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