Dicer1 and miR-219 Are required for normal oligodendrocyte differentiation and myelination.
Dicer1 and miR-219 Are required for normal oligodendrocyte differentiation and myelination.
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Dicer1 和 miR-219 是正常少突胶质细胞分化和髓鞘形成所必需的。
DOI：
10.1016/j.neuron.2010.01.027
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发表时间：
2010-03-11
期刊：
影响因子：
16.2
通讯作者：
Barres BA
中科院分区：
文献类型：
--
作者：
Dugas JC;Cuellar TL;Scholze A;Ason B;Ibrahim A;Emery B;Zamanian JL;Foo LC;McManus MT;Barres BA
为了研究microRNAs在调节少突胶质细胞(OL)分化和髓鞘形成中的作用，我们使用了转基因小鼠，在转基因小鼠中，OPC和OL中的microRNA加工被靶向缺失Dicer1破坏。我们发现，抑制OPC-OL miRNA的处理扰乱了正常的中枢神经系统髓鞘形成，并且缺乏成熟miRNAs的OPC在体外无法正常分化。我们鉴定了三个miRNAs，miR-219，miR-138和miR-338，它们在OL分化过程中被诱导10-100倍，其中最强的miR-219是促进OL分化所必需的且充分的，并部分修复了由于全部miRNA丢失而导致的OL分化缺陷。MIR-219直接抑制PDGFFRα、Sox6、FoxJ3和ZFP 238蛋白的表达，这些蛋白在正常情况下都有助于促进OPC的增殖。综上所述，这些发现表明miR-219在OL谱系的分化和增殖抑制的耦合中发挥关键作用，使OPC从增殖的OPC快速转变为髓鞘OPC。
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 PDGFRα, 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.
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影响因子：
4.8
作者：
Izzotti, Alberto;Calin, George A.;De Flora, Silvio
通讯作者：
De Flora, Silvio
影响因子：
5.3
作者：
Davis, Tigwa H.;Cuellar, Trinna L.;Ullian, Erik M.
通讯作者：
Ullian, Erik M.
影响因子：
4.3
作者：
Carleton, Michael;Cleary, Michele A.;Linsley, Peter S.
通讯作者：
Linsley, Peter S.
影响因子：
5.3
作者：
Assanah, Marcela;Lochhead, Richard;Canoll, Peter
通讯作者：
Canoll, Peter
DOI：
10.1073/pnas.0801689105
发表时间：
2008-04-08
影响因子：
11.1
作者：
Cuellar, Trinna L.;Davis, Tigwa H.;McManus, Michael T.
通讯作者：
McManus, Michael T.