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.
N1 - Funding Information:
The brain tissue App-Ps1 datasets was kindly supplied by Koen Bossers and Joost Verhaagen. The microglia illustrations were generated by Hilmar van Weering. This work was supported by funds from the Internationale Stichting Alzheimer Onderzoek [ISAO 08504 and 12509], NANONET COST [BM1002], the Netherlands Organization for Scientific Research [NWO; VICI], the Graduate School of Medical Sciences of the University Medical Center Groningen and the Dutch Hersenstichting. The authors acknowledge technical support by the FACS facility of the University Medical Center Groningen.
PY - 2015/5/23
Y1 - 2015/5/23
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.
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U2 - 10.1186/s40478-015-0203-5
DO - 10.1186/s40478-015-0203-5
M3 - Article
C2 - 26001565
AN - SCOPUS:85018223217
VL - 3
SP - 31
JO - Acta neuropathologica communications
JF - Acta neuropathologica communications
SN - 2051-5960
ER -