Control of oligodendroglial cell number by the miR-17-92 cluster

Control of oligodendroglial cell number by the miR-17-92 cluster
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DOI:
10.1242/dev.050633
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发表时间:
2010-07-01
期刊:
影响因子:
4.6
通讯作者:
Simons, Mikael
Simons, Mikael
中科院分区:
生物学2区
文献类型:
--
作者:
Budde, Holger;Schmitt, Sebastian;Simons, Mikael

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中枢神经系统中的骨髓细胞的产生需要在少突胶质细胞中启动特定的基因表达程序。我们认为microRNA(miRNA)可以通过调节关键发育基因来在此过程中发挥重要作用。培养的少突胶质细胞的微阵列分析将miR-17-92 miRNA簇确定为高度富集的少突胶质细胞。我们使用2',3'-循环核苷酸3'磷酸二酯酶(CNP) - 晶状体小鼠在少突胶质细胞中特别删除了miR-17-92簇。缺乏miR-17-92导致体内少突胶质细胞数的减少,我们发现这些miRNA在少突胶质细胞前体细胞原代培养物中的表达通过影响AKT信号传导促进细胞增殖。总之,这些结果表明miRNA途径对于确定寡头细胞数量至关重要,并且miR-17-92簇在此过程中至关重要。
The generation of myelinating cells in the central nervous system requires the initiation of specific gene expression programs in oligodendrocytes. We reasoned that microRNAs (miRNAs) could play an important role in this process by regulating crucial developmental genes. Microarray profiling of cultured oligodendrocytes identified the miR-17-92 miRNA cluster as highly enriched in oligodendrocytes. We specifically deleted the miR-17-92 cluster in oligodendrocytes using 2',3'-cyclic nucleotide 3' phosphodiesterase (Cnp)-Cre mice. Absence of miR-17-92 leads to a reduction in oligodendrocyte number in vivo and we find that the expression of these miRNAs in primary cultures of oligodendrocyte precursor cells promotes cell proliferation by influencing Akt signaling. Together, these results suggest that the miRNA pathway is essential in determining oligodendroglial cell number and that the miR-17-92 cluster is crucial in this process.