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微小RNA介导的体细胞重编程为神经干细胞或神经元

MicroRNA-Mediated Reprogramming of Somatic Cells into Neural Stem Cells or Neurons.

作者信息

Yang Hao, Zhang Lingling, An Jing, Zhang Qian, Liu Cuicui, He Baorong, Hao Ding-Jun

机构信息

Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi, 710054, China.

Department of Spine Surgery, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi, 710054, China.

出版信息

Mol Neurobiol. 2017 Mar;54(2):1587-1600. doi: 10.1007/s12035-016-0115-9. Epub 2016 Sep 22.

DOI:10.1007/s12035-016-0115-9
PMID:27660263
Abstract

Cellular reprogramming is a promising strategy to generate neural stem cells (NSCs) or desired subtype-specific neurons for cell-based therapeutic intervention. By far, the intricate cell event like reprogramming of non-neural cells to desired cell types can be achieved by forced expression of lineage-related transcription factors (TFs), nuclear transfer, a defined set of factors, and via non-coding microRNAs (miRNAs), as well as other precisely defined conditions. In addition, scientists have been trying to develop better approaches for reprogramming, either by using distinct combinations of a set of small molecules and certain TFs or delivery of appropriate small molecules and miRNAs. The miRNA-mediated approach is fascinating because of its potential to rapidly generate a variety of therapeutically desired cell types from other cell lineages. Recent studies have made great progress in miRNA-mediated neural reprogramming of somatic cells to various specific neuronal subtypes with more efficiency even though the exact mechanisms remain to be further explored. Based on key roles of miRNAs in neural reprogramming across differentiated cell lineages, it is of vital interest to summarize the recent knowledge regarding the instructive role of miRNAs in direct conversion of somatic cells into neural lineages. This precise review mainly focuses on recent discoveries of miRNAs functions in initiating cell reprogramming and fate specification of the neuronal subtype. Moreover, we discuss most recent findings about some miRNAs' activity in regulating various developmental stages of neurons, which is helpful for understanding the event network between miRNAs and their targets.

摘要

细胞重编程是一种很有前景的策略,可用于生成神经干细胞(NSCs)或所需的亚型特异性神经元,以进行基于细胞的治疗干预。到目前为止,通过强制表达谱系相关转录因子(TFs)、核移植、一组特定的因子、非编码微小RNA(miRNAs)以及其他精确界定的条件,可以实现诸如将非神经细胞重编程为所需细胞类型这样复杂的细胞事件。此外,科学家们一直在尝试开发更好的重编程方法,要么使用一组小分子和某些TFs的不同组合,要么递送合适的小分子和miRNAs。miRNA介导的方法因其有可能从其他细胞谱系快速生成各种治疗所需的细胞类型而备受关注。尽管确切机制仍有待进一步探索,但最近的研究在miRNA介导的将体细胞重编程为各种特定神经元亚型方面取得了很大进展,且效率更高。基于miRNAs在跨分化细胞谱系的神经重编程中的关键作用,总结关于miRNAs在将体细胞直接转化为神经谱系中的指导作用的最新知识至关重要。这篇精确的综述主要关注miRNAs在启动细胞重编程和神经元亚型命运特化方面功能的最新发现。此外,我们讨论了关于一些miRNAs在调节神经元不同发育阶段活性的最新发现,这有助于理解miRNAs与其靶标之间的事件网络。

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