Identification of genes preferentially expressed by microglia and upregulated during cuprizone-induced inflammation

Identification of genes preferentially expressed by microglia and upregulated during cuprizone-induced inflammation
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DOI:
10.1002/glia.20477
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发表时间:
2007-06-01
期刊:
影响因子:
6.2
通讯作者:
Vallieres, Luc
Vallieres, Luc
中科院分区:
医学1区
文献类型:
--
作者:
Bedard, Andreanne;Tremblay, Pierrot;Vallieres, Luc

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小胶质细胞、单核细胞和外周巨噬细胞有着共同的起源和许多特征,但在基因表达水平上将它们彼此区分开来的是什么仍然在很大程度上未知。在这项研究中,我们比较了新鲜纯化的小胶质细胞,单核细胞和脾巨噬细胞的转录谱,使用Affyssin小鼠基因组阵列,以确定主要由小胶质细胞表达的基因。在数以万计的基因分析,127个潜在的候选人被发现,包括9个新发现的基因编码质膜和胞外蛋白。在大脑中,后者选择性地表达的小胶质细胞,如原位杂交所揭示的。与检查的其他组织相比,其中三种被确认为仅在脑中表达(MSR 2)或主要在脑中表达(GPR 12、GPR 34)。此外,所有这些基因在用脱髓鞘毒素cuprizone处理后在活化的小胶质细胞中上调,表明它们在神经炎症中发挥作用。总之,本研究报告了新的选择性标记小胶质细胞,这应该证明是有用的,不仅要识别和分离这些细胞,而且要更好地了解其独特的性能。(c)2007 Wiley-Liss,Inc.
Microglia, monocytes, and peripheral macrophages share a common origin and many characteristics, but what distinguishes them from each other at the level of gene expression remains largely unknown. In this study, we compared the transcriptional profiles of freshly purified microglia, monocytes, and spleen macrophages using Affymetrix Mouse Genome arrays to identify genes predominantly expressed by microglia. Among tens of thousands of genes assayed, 127 potential candidates were found, including nine newly discovered genes encoding plasma membrane and extracellular proteins. In the brain, the latter were selectively expressed by microglia, as revealed by in situ hybridization. Three of them were confirmed to be exclusively (MSR2) or predominantly (GPR12, GPR34) expressed in the brain compared to the other tissues examined. Furthermore, all of these genes were upregulated in activated microglia after treatment with the demyelinating toxin cuprizone, suggesting that they play roles in neuroinflammation. In conclusion, this study reports the identification of new selective markers for microglia, which should prove useful not only to identify and isolate these cells, but also to better understand their distinctive properties. (c) 2007 Wiley-Liss, Inc.