Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: a co-expression meta-analysis

TY - JOUR

T1 - Induction of a common microglia gene expression signature by aging and neurodegenerative conditions

T2 - a co-expression meta-analysis

AU - Holtman, Inge R

AU - Raj, Divya D

AU - Miller, Jeremy A

AU - Schaafsma, Wandert

AU - Yin, Zhuoran

AU - Brouwer, Nieske

AU - Wes, Paul D

AU - Möller, Thomas

AU - Orre, Marie

AU - Kamphuis, Willem

AU - Hol, Elly M

AU - Boddeke, Erik W G M

AU - Eggen, Bart J L

PY - 2015

Y1 - 2015

N2 - INTRODUCTION: 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).RESULTS: 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.CONCLUSION: Microglia priming induces a highly conserved transcriptional signature with aging- and disease-specific aspects.

AB - INTRODUCTION: 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).RESULTS: 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.CONCLUSION: Microglia priming induces a highly conserved transcriptional signature with aging- and disease-specific aspects.

U2 - 10.1186/s40478-015-0203-5

DO - 10.1186/s40478-015-0203-5

M3 - Article

C2 - 26001565

SN - 2051-5960

VL - 3

SP - 31

JO - Acta neuropathologica communications

JF - Acta neuropathologica communications

ER -