Institute of Neuroscience, Fourth Military Medical University, Xi'an 710032, China.
Mol Biol Cell. 2012 Aug;23(15):2867-78. doi: 10.1091/mbc.E12-04-0270. Epub 2012 Jun 13.
The generation of myelinating cells from multipotential neural stem cells in the CNS requires the initiation of specific gene expression programs in oligodendrocytes (OLs). We reasoned that microRNAs (miRNAs) could play an important role in this process by regulating genes crucial for OL development. Here we identified miR-7a as one of the highly enriched miRNAs in oligodendrocyte precursor cells (OPCs), overexpression of which in either neural progenitor cells (NPCs) or embryonic mouse cortex promoted the generation of OL lineage cells. Blocking the function of miR-7a in differentiating NPCs led to a reduction in OL number and an expansion of neuronal populations simultaneously. We also found that overexpression of this miRNA in purified OPC cultures promoted cell proliferation and inhibited further maturation. In addition, miR-7a might exert the effects just mentioned partially by directly repressing proneuronal differentiation factors including Pax6 and NeuroD4, or proOL genes involved in oligodendrocyte maturation. These results suggest that miRNA pathway is essential in determining cell fate commitment for OLs and thus providing a new strategy for modulating this process in OL loss diseases.
从中枢神经系统的多能神经干细胞生成髓鞘细胞需要在少突胶质细胞(OLs)中启动特定的基因表达程序。我们推断,microRNAs(miRNAs)可以通过调节 OL 发育关键基因在这个过程中发挥重要作用。在这里,我们鉴定出 miR-7a 是少突胶质前体细胞(OPCs)中高度富集的 miRNAs 之一,其在神经祖细胞(NPCs)或胚胎鼠皮层中的过表达促进了 OL 谱系细胞的生成。在分化中的 NPCs 中阻断 miR-7a 的功能会导致 OL 数量减少和神经元群体同时扩张。我们还发现,在纯化的 OPC 培养物中过表达这种 miRNA 会促进细胞增殖并抑制进一步成熟。此外,miR-7a 可能通过直接抑制包括 Pax6 和 NeuroD4 在内的神经前体细胞分化因子或参与少突胶质细胞成熟的 proOL 基因来部分发挥上述作用。这些结果表明,miRNA 途径对于 OL 细胞命运决定至关重要,从而为调节 OL 丢失疾病中的这一过程提供了新的策略。