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首页> 外文期刊>Neuron >Dicer1 and miR-219 Are required for normal oligodendrocyte differentiation and myelination.
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Dicer1 and miR-219 Are required for normal oligodendrocyte differentiation and myelination.

机译：Dicer1和miR-219是正常少突胶质细胞分化和髓鞘形成所必需的。

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摘要

To investigate the role of microRNAs in regulating oligodendrocyte (OL) differentiation and myelination, we utilized transgenic mice in which microRNA processing was disrupted in OL precursor cells (OPCs) and OLs by targeted deletion of Dicer1. We found that inhibition of OPC-OL miRNA processing disrupts normal CNS myelination and that OPCs lacking mature miRNAs fail to differentiate normally in vitro. We identified three miRNAs (miR-219, miR-138, and miR-338) that are induced 10-100x during OL differentiation; the most strongly induced of these, miR-219, is necessary and sufficient to promote OL differentiation, and partially rescues OL differentiation defects caused by total miRNA loss. miR-219 directly represses the expression of PDGFRalpha, Sox6, FoxJ3, and ZFP238 proteins, all of which normally help to promote OPC proliferation. Together, these findings show that miR-219 plays a critical role in coupling differentiation to proliferation arrest in the OL lineage, enabling the rapid transition from proliferating OPCs to myelinating OLs.
机译：为了研究microRNA在调节少突胶质细胞（OL）分化和髓鞘形成中的作用，我们利用了转基因小鼠，其中通过Dicer1的靶向缺失，在OL前体细胞（OPC）和OL中破坏了microRNA的加工。我们发现抑制OPC-OL miRNA加工会破坏正常的CNS髓鞘形成，而缺乏成熟miRNA的OPC无法在体外正常分化。我们鉴定了三种在OL分化过程中被诱导10-100x的miRNA（miR-219，miR-138和miR-338）。其中最强烈诱导的miR-219是促进OL分化所必需的，并且足以挽救由总miRNA丢失引起的OL分化缺陷。 miR-219直接抑制PDGFRalpha，Sox6，FoxJ3和ZFP238蛋白的表达，所有这些蛋白通常都有助于促进OPC增殖。总之，这些发现表明，miR-219在将分化与OL谱系中的增殖停滞偶联中起着至关重要的作用，从而使OPC从增殖的OPC迅速转变为有髓的OL。

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