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MicroRNA miR-204 regulates proliferation and differentiation of oligodendroglia in culture.
Glia ( IF 5.4 ) Pub Date : 2020-03-16 , DOI: 10.1002/glia.23821
Jan Wittstatt 1 , Matthias Weider 1 , Michael Wegner 1 , Simone Reiprich 1
Affiliation  

Oligodendrocytes wrap and physically shield axons of the central nervous system with myelin sheaths, resulting in rapid signal transduction and accurate neuronal function. The complex oligodendroglial development from immature oligodendrocyte precursor cells (OPCs) to myelinating oligodendrocytes (OLs) is profoundly dependent on the activity of transcription factors of the Sox protein family. Target genes of the crucial regulator Sox10 have recently been expanded to microRNAs. Here, we report miR‐204 as a novel transcriptional target of Sox10. Regulatory regions of miR‐204 show responsiveness to and binding of Sox10 in reporter gene assays and electromobility shift assays. Once expressed, miR‐204 inhibits OPC proliferation and facilitates differentiation into OLs in the presence of Sox10 as evident from overexpression in primary rat and mouse oligodendroglial cultures. Phenotypes are at least in part caused by miR‐204‐dependent repression of the pro‐proliferative Ccnd2 and the differentiation inhibiting Sox4. These findings argue that the transcriptional activator Sox10 forces oligodendroglial cells to exit the cell cycle and start differentiation by gene inhibition via miR‐204 induction.

中文翻译:

MicroRNA miR-204 调节培养中少突胶质细胞的增殖和分化。

少突胶质细胞用髓鞘包裹并物理屏蔽中枢神经系统的轴突,从而实现快速信号转导和准确的神经元功能。从未成熟的少突胶质细胞前体细胞 (OPCs) 到有髓少突胶质细胞 (OLs) 的复杂少突胶质细胞发育严重依赖于 Sox 蛋白家族转录因子的活性。关键调节因子 Sox10 的靶基因最近已扩展到 microRNA。在这里,我们报告了 miR-204 作为 Sox10 的新转录靶点。miR-204 的调控区域在报告基因检测和电动迁移检测中显示出对 Sox10 的响应和结合。一经表态,miR-204 在 Sox10 存在的情况下抑制 OPC 增殖并促进分化为 OL,这从原代大鼠和小鼠少突胶质细胞培养物中的过表达中可以看出。表型至少部分是由 miR-204 依赖性抑制促增殖 Ccnd2 和分化抑制 Sox4 引起的。这些发现认为转录激活剂 Sox10 迫使少突胶质细胞退出细胞周期并通过 miR-204 诱导的基因抑制开始分化。
更新日期:2020-03-16
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