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微小RNA介导的神经干细胞增殖、谱系分化及凋亡调控

MicroRNA-mediated regulation of proliferation, lineage differentiation, and apoptosis in neural stem cells.

作者信息

Lee Yukyeong, Boschian Camilla, Ko Kinarm

机构信息

Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Republic of Korea.

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.

出版信息

RNA Biol. 2025 Dec;22(1):1-17. doi: 10.1080/15476286.2025.2558631. Epub 2025 Sep 15.

DOI:10.1080/15476286.2025.2558631
PMID:40924462
Abstract

Neural stem cells (NSCs) are multipotent stem cells with self-renewal capacity, able to differentiate into all neural lineages of the central nervous system, including neurons, oligodendrocytes, and astrocytes; thus, their proliferation and differentiation are essential for embryonic neurodevelopment and adult brain homoeostasis. Dysregulation in these processes is implicated in neurological disorders, highlighting the need to elucidate how NSCs proliferate and differentiate to clarify the mechanisms of neurogenesis and uncover potential therapeutic targets. MicroRNAs (miRNAs) are small, post-transcriptional regulators of gene expression involved in many aspects of nervous system development and function. Multiple studies have shown that miRNAs control the balance between self-renewal and differentiation during development through transcriptional networks and fine-tuned signalling pathways. They also regulate key biological processes, including cell fate determination, developmental timing, neurogenesis, gliogenesis, and apoptosis. Transcriptomic analyses and high-resolution profiling have revealed temporally and spatially restricted miRNA expression patterns in NSCs and their progeny, suggesting highly context-dependent regulatory functions. Here, we provide an integrated overview of recent advances in miRNA biology relevant to NSC maintenance and lineage specification, with a focus on the mechanistic understanding of miRNA roles in neuronal differentiation, glial development, and programmed cell death across neural development.

摘要

神经干细胞(NSCs)是具有自我更新能力的多能干细胞,能够分化为中枢神经系统的所有神经谱系,包括神经元、少突胶质细胞和星形胶质细胞;因此,它们的增殖和分化对于胚胎神经发育和成年大脑稳态至关重要。这些过程中的失调与神经疾病有关,这突出表明需要阐明神经干细胞如何增殖和分化,以阐明神经发生的机制并发现潜在的治疗靶点。微小RNA(miRNAs)是参与神经系统发育和功能多个方面的基因表达的小型转录后调节因子。多项研究表明,微小RNA通过转录网络和微调的信号通路在发育过程中控制自我更新和分化之间的平衡。它们还调节关键的生物学过程,包括细胞命运决定、发育时间、神经发生、胶质细胞生成和细胞凋亡。转录组分析和高分辨率图谱揭示了神经干细胞及其后代中微小RNA在时间和空间上受限的表达模式,表明其具有高度依赖于上下文的调节功能。在这里,我们提供了与神经干细胞维持和谱系特化相关的微小RNA生物学最新进展的综合概述,重点是对微小RNA在整个神经发育过程中神经元分化、胶质细胞发育和程序性细胞死亡中的作用的机制理解。

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本文引用的文献

1
Exosomes enriched with miR-124-3p show therapeutic potential in a new microfluidic triculture model that recapitulates neuron-glia crosstalk in Alzheimer's disease.富含miR-124-3p的外泌体在一种新的微流控共培养模型中显示出治疗潜力,该模型概括了阿尔茨海默病中的神经元-神经胶质细胞相互作用。
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MiRNAs as major players in brain health and disease: current knowledge and future perspectives.微小RNA作为大脑健康与疾病的主要参与者:当前认知与未来展望
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regulates the proliferation and differentiation of neural stem/progenitor cells.
调节神经干/祖细胞的增殖和分化。
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Recent Advances in the miRNA-Mediated Regulation of Neuronal Differentiation and Death.微小RNA介导的神经元分化与死亡调控的最新进展
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Lowering Hippocampal miR-29a Expression Slows Cognitive Decline and Reduces Beta-Amyloid Deposition in 5×FAD Mice.降低海马体 miR-29a 表达可减缓认知衰退并减少 5×FAD 小鼠的β-淀粉样蛋白沉积。
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SOD1 Astrocyte-Derived Extracellular Vesicles Induce Motor Neuron Death by a miRNA-155-5p-Mediated Mechanism.SOD1 星形细胞衍生的细胞外囊泡通过 miRNA-155-5p 介导的机制诱导运动神经元死亡。
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