Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: a co-expression meta-analysis.
Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: a co-expression meta-analysis.
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DOI：
10.1186/s40478-015-0203-5
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发表时间：
2015-05-23
影响因子：
7.1
通讯作者：
Eggen BJ
中科院分区：
文献类型：
--
作者：
Holtman IR;Raj DD;Miller JA;Schaafsma W;Yin Z;Brouwer N;Wes PD;Möller T;Orre M;Kamphuis W;Hol EM;Boddeke EW;Eggen BJ
小胶质细胞是中枢神经系统的组织巨噬细胞，可监测大脑稳态并对神经元损伤和压力做出反应。衰老和神经退行性疾病会诱发过敏性促炎表型，称为引发的小胶质细胞。为了确定启动的基因表达特征，使用加权基因共表达网络分析 (WGCNA) 比较了衰老、阿尔茨海默病 (AD) 和肌萎缩侧索硬化症 (ALS) 小鼠模型中小胶质细胞的转录组。鉴定出高度一致的上调基因一致转录谱，其与脂多糖（LPS）诱导的急性炎症基因网络显着不同。在急性炎症网络中 NF-κB 信号传导显着富集的情况下，引发的小胶质细胞图谱包含与吞噬体、溶酶体、抗原呈递和 AD 信号传导相关的关键特征。此外，还确定了衰老、AD 和 ALS 的特定特征。小胶质细胞启动诱导具有衰老和疾病特异性的高度保守的转录特征。本文的在线版本 (doi:10.1186/s40478-015-0203-5) 包含补充材料，可供授权用户使用。
Microglia are tissue macrophages of the central nervous system that monitor brain homeostasis and react upon neuronal damage and stress. Aging and neurodegeneration induce a hypersensitive, pro-inflammatory phenotype, referred to as primed microglia. To determine the gene expression signature of priming, the transcriptomes of microglia in aging, Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS) mouse models were compared using Weighted Gene Co-expression Network Analysis (WGCNA). A highly consistent consensus transcriptional profile of up-regulated genes was identified, which prominently differed from the acute inflammatory gene network induced by lipopolysaccharide (LPS). Where the acute inflammatory network was significantly enriched for NF-κB signaling, the primed microglia profile contained key features related to phagosome, lysosome, antigen presentation, and AD signaling. In addition, specific signatures for aging, AD, and ALS were identified. Microglia priming induces a highly conserved transcriptional signature with aging- and disease-specific aspects. The online version of this article (doi:10.1186/s40478-015-0203-5) contains supplementary material, which is available to authorized users.
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WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
5.3
作者：
Hickman, Suzanne E.;Allison, Elizabeth K.;El Khoury, Joseph
通讯作者：
El Khoury, Joseph
影响因子：
9.3
作者：
Cribbs DH;Berchtold NC;Perreau V;Coleman PD;Rogers J;Tenner AJ;Cotman CW
通讯作者：
Cotman CW
DOI：
10.1073/pnas.95.18.10896
发表时间：
1998-09-01
影响因子：
11.1
作者：
Harrison, JK;Jiang, Y;Feng, LL
通讯作者：
Feng, LL
DOI：
10.1126/science.1252945
发表时间：
2014-10-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Baruch K;Deczkowska A;David E;Castellano JM;Miller O;Kertser A;Berkutzki T;Barnett-Itzhaki Z;Bezalel D;Wyss-Coray T;Amit I;Schwartz M
通讯作者：
Schwartz M