Identification of Tmem10 as a novel late-stage oligodendrocytes marker for detecting hypomyelination.

Identification of Tmem10 as a novel late-stage oligodendrocytes marker for detecting hypomyelination.
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DOI:
10.7150/ijbs.7526
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发表时间:
2013
影响因子:
9.2
通讯作者:
Chen M
Chen M
中科院分区:
生物学2区
文献类型:
--
作者:
Jiang W;Yang W;Yang W;Zhang J;Pang D;Gan L;Luo L;Fan Y;Liu Y;Chen M

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少突胶质细胞包裹轴突,形成致密的绝缘多层结构,称为髓鞘。Tmem10是一种新型的I型跨膜糖蛋白,在少突胶质细胞中高度表达,其生物学功能在很大程度上仍然未知。此外,Tmem10的表达模式仍然存在一些争议。由于其表达模式的不一致性和缺乏有效的特异性抗体,Tmem10没有被广泛接受为成熟少突胶质细胞的标志物。作为解决这些问题的一种手段,并帮助少突胶质细胞相关疾病的未来研究,我们已经产生了高度特异性的Tmem10抗体。使用这种Tmem10抗体,我们阐明了Tmem10蛋白在出生后2周时首先在小鼠大脑中表达,并随年龄增加,仅在中枢神经系统(CNS)中表达。我们还揭示了Tmem10在晚期少突胶质细胞中特异性表达,并且晚于晚期髓鞘标记物MAG。最后,我们发现Tmem10与MOG和MBP阳性髓鞘纤维共表达,并且在髓鞘形成不足的小鼠模型中显著减少。总之,我们的研究表明,Tmem10可以用作髓鞘形成少突胶质细胞的特异性标志物,并可能用于评价髓鞘形成疾病,如多发性硬化症。
Oligodendrocytes ensheath axons to form compact insulating multilamellar structures known as myelin. Tmem10 is a novel type I transmembrane glycoprotein that is highly expressed in oligodendrocytes and whose biological function remains largely unknown. Furthermore, the expression pattern of Tmem10 remains a matter of some controversy. Given the inconsistency of its expression pattern and the lack of validated specific antibodies, Tmem10 is not widely accepted as a marker for mature oligodendrocytes. As a means to solve these problems and to aid future studies of oligodendrocyte-associated diseases, we have generated a highly specific Tmem10 antibody. Using this Tmem10 antibody, we clarify that Tmem10 protein is firstly expressed at 2 weeks in the postnatal mouse brain with age-related increase, only in the central nervous system (CNS). We also reveal that Tmem10 is expressed specifically in late stage oligodendrocytes and later than MAG, a late-stage myelin marker. Finally, we show that Tmem10 co-expresses with MOG- and MBP-positive myelin fibers and is dramatically reduced in a hypomyelination mouse model. In conclusion, our study demonstrates that Tmem10 can be used as a specific marker for myelinating oligodendrocytes and perhaps for the evaluation of myelination diseases, such as multiple sclerosis.
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