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首页> 外文期刊>Cell Reports >A Neurodegeneration-Specific Gene-Expression Signature of Acutely Isolated Microglia from an Amyotrophic Lateral Sclerosis Mouse Model
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A Neurodegeneration-Specific Gene-Expression Signature of Acutely Isolated Microglia from an Amyotrophic Lateral Sclerosis Mouse Model

机译：急性分离的小胶质细胞从肌萎缩性侧索硬化症小鼠模型的神经变性特定基因表达签名。

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Microglia are resident immune cells of the CNS that are activated by infection, neuronal injury, and inflammation. Here, we utilize flow cytometry and deep RNA sequencing of acutely isolated spinal cord microglia to define their activation in vivo. Analysis of resting microglia identified 29 genes that distinguish microglia from other CNS cells and peripheral macrophages/monocytes. We then analyzed molecular changes in microglia during neurodegenerative disease activation using the SOD1^G^9^3^A mouse model of amyotrophic lateral sclerosis (ALS). We found that SOD1^G^9^3^A microglia are not derived from infiltrating monocytes, and that both potentially neuroprotective and toxic factors, including Alzheimer's disease genes, are concurrently upregulated. Mutant microglia differed from SOD1^W^T, lipopolysaccharide-activated microglia, and M1/M2 macrophages, defining an ALS-specific phenotype. Concurrent messenger RNA/fluorescence-activated cell sorting analysis revealed posttranscriptional regulation of microglia surface receptors and T cell-associated changes in the transcriptome. These results provide insights into microglia biology and establish a resource for future studies of neuroinflammation.
机译：小胶质细胞是中枢神经系统的驻留免疫细胞，可通过感染，神经元损伤和炎症激活。在这里，我们利用流式细胞仪和急性分离的脊髓小胶质细胞的深RNA测序来定义它们在体内的激活。对静息小胶质细胞的分析确定了29个基因，这些基因将小胶质细胞与其他CNS细胞和外周巨噬细胞/单核细胞区分开。然后，我们使用肌萎缩性侧索硬化症（ALS）的SOD1 ^ G ^ 9 ^ 3 ^ A小鼠模型分析了神经退行性疾病激活过程中小胶质细胞的分子变化。我们发现SOD1 ^ G ^ 9 ^ 3 ^ A小胶质细胞不是来自浸润的单核细胞，并且潜在的神经保护和毒性因子（包括阿尔茨海默氏病基因）同时被上调。突变的小胶质细胞不同于SOD1 ^ W ^ T，脂多糖激活的小胶质细胞和M1 / M2巨噬细胞，定义了ALS特异性表型。并发信使RNA /荧光激活细胞分选分析揭示了小胶质细胞表面受体的转录后调控和转录组中与T细胞相关的变化。这些结果提供了对小胶质细胞生物学的见识，并为以后的神经炎症研究提供了资源。

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