Microglia, a potential source of neurons, astrocytes, and oligodendrocytes
Microglia, a potential source of neurons, astrocytes, and oligodendrocytes
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DOI：
10.1002/glia.10306
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发表时间：
2004-01
期刊：
影响因子：
6.2
通讯作者：
A. Yokoyama;Lihua Yang;Suzuka Itoh;Kohji Mori;Junya Tanaka
中科院分区：
文献类型：
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作者：
A. Yokoyama;Lihua Yang;Suzuka Itoh;Kohji Mori;Junya Tanaka
小胶质细胞被认为是大脑中唯一的中胚层来源的细胞群，尽管它们的作用还没有完全了解。本研究表明，大鼠原代小胶质细胞表达巢蛋白，A2B5和O4抗原，这是少突胶质细胞前体细胞的标志物。基于这些发现，我们研究了小胶质细胞是否产生神经元或大胶质细胞。将纯化的小胶质细胞在10%胎牛血清存在下培养3天，然后在70%血清存在下培养2天。在两步培养过程中，小胶质细胞高度增殖，并强烈表达DNA结合（Id）基因的抑制剂，表明细胞的去分化。去分化的细胞还表达促进分化为神经元或大胶质细胞的转录因子。当将去分化细胞转移到聚L赖氨酸包被的基底上的无血清培养基中时，大量细胞迅速转变为长突起携带细胞，其表达微管相关蛋白2、突触蛋白I、神经丝蛋白、胶质细胞酸性蛋白或半乳糖苷。当小胶质细胞通过乙酰化低密度脂蛋白（LDL）受体或通过吞噬依赖性机制进行荧光标记时，观察到带有荧光的神经元、星形胶质细胞或少突胶质细胞。神经球，神经干细胞的聚集体，表达Musashi 1和表皮生长因子受体，但小胶质细胞衍生的细胞没有。这些结果表明小胶质细胞作为多能干细胞产生神经元、星形胶质细胞或少突胶质细胞的新作用。© 2003 Wiley利斯公司
Microglia are considered the only cell population of mesodermal origin in the brain, although their role is not fully understood. The present study demonstrated that rat primary microglial cells expressed nestin, A2B5, and O4 antigens, which are markers for oligodendrocyte precursor cells. Based on these findings, we investigated whether microglial cells generated neurons or macroglial cells. Purified microglial cells were cultured in the presence of 10% fetal bovine serum for 3 days, followed by culture in the presence of 70% serum for 2 days. During the two‐step culture, microglial cells became highly proliferative and strongly expressed inhibitor of DNA binding (Id) genes, indicative of dedifferentiation of the cells. The dedifferentiated cells also expressed transcription factors that promote differentiation into neurons or macroglial cells. When the dedifferentiated cells were transferred into serum‐free medium on poly‐L‐lysine‐coated substrate, a substantial number of the cells rapidly turned into long process‐bearing cells, which expressed microtubule‐associated protein 2, synapsin I, neurofilament proteins, glial fibrillary acidic protein, or galactocerebroside. When microglial cells were fluorescently labeled through acetylated low‐density lipoprotein (LDL) receptors or by a phagocytosis‐dependent mechanism, fluorescence‐bearing neurons, astrocytes, or oligodendrocytes were observed. Neurospheres, aggregates of neural stem cells, expressed Musashi 1 and epidermal growth factor receptor, but the microglia‐derived cells did not. These results suggest a novel role of microglia as multipotential stem cells to give rise to neurons, astrocytes, or oligodendrocytes. © 2003 Wiley‐Liss, Inc.