A novel oligodendrocyte cell line OLP6 shows the successive stages of oligodendrocyte development: Late progenitor, immature and mature stages
A novel oligodendrocyte cell line OLP6 shows the successive stages of oligodendrocyte development: Late progenitor, immature and mature stages
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DOI：
10.1016/j.neuroscience.2005.07.011
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发表时间：
2005-12
期刊：
影响因子：
3.3
通讯作者：
T. Matsushita;Y. Amagai;T. Soga;K. Terai;Masuo Obinata;S. Hashimoto
中科院分区：
文献类型：
--
作者：
T. Matsushita;Y. Amagai;T. Soga;K. Terai;Masuo Obinata;S. Hashimoto
用阶段特异性抗体详细研究了从少突胶质前体细胞到成熟少突胶质细胞的连续发育阶段。然而，目前还没有从少突胶质祖细胞向成熟少突胶质细胞逐步分化的细胞系。在这里，我们展示了从携带温度敏感型猿猴病毒40大T抗原基因的成年转基因大鼠建立的永生化少突胶质细胞系OLP6。OLP6细胞呈成纤维细胞形态，在33℃条件下持续增殖，39℃培养时呈生长停滞和多极形态，表达少突胶质细胞标志物O4，2‘-3’-环核苷酸3‘-磷酸二酯酶、半乳糖脑苷脂和第二内皮细胞分化基因受体-2。这些结果表明，内皮分化基因受体-2的激活对OLP6细胞具有抗凋亡和髓鞘生成的作用。综上所述，通过改变培养温度，处于少突胶质前体细胞晚期的OLP6细胞可以进展到未成熟的少突胶质细胞阶段。此外，溶血磷脂酸还能促进未成熟少突胶质细胞的成熟。这种OLP6细胞应该为研究少突胶质细胞逐步分化的精确机制提供了一个有效的模型系统。
The successive stages of development from oligodendrocyte progenitor to mature oligodendrocyte have been investigated in detail by using stage-specific antibodies. However, no cell lines are available that show stepwise differentiation from oligodendrocyte progenitors to mature oligodendrocytes. Here we show the establishment of an immortalized oligodendrocyte cell line, OLP6, from adult transgenic rats harboring the temperature-sensitive simian virus 40 large T-antigen gene. The OLP6 cells had a fibroblastic morphology and continuously proliferated at 33°C. They displayed growth arrest and multipolar morphology when they were cultured at 39°C. They express the oligodendrocytic markers O4, 2′-3′-cyclic-nucleotide 3′-phosphodiesterase, galactocerebroside and second endothelial differentiation gene receptor-2 at 39°C. The OLP6 cells underwent apoptosis upon serum withdrawal at 39°C. Lysophosphatidic acid inhibited this apoptosis and promoted the expression of myelin basic protein. These results demonstrate that the activation of endothelial differentiation gene receptor-2 exerts anti-apoptosis and myelinogenesis effects on the OLP6 cells. Taken together, the OLP6 cells in the late oligodendrocyte progenitor stage can progress to the immature oligodendrocyte stage by shifting culture temperature. Furthermore, lysophosphatidic acid promoted the maturation of OLP6 cells in the immature oligodendrocyte stage. Such OLP6 cells should provide a potent model system for studying the precise mechanism involved in stepwise differentiation of oligodendrocytes.