A Neurodegeneration-Specific Gene-Expression Signature of Acutely Isolated Microglia from an Amyotrophic Lateral Sclerosis Mouse Model

被引：511

作者：

Chiu, Isaac M. ^{[1
,2
]}

Morimoto, Emiko T. A. ^{[3
]}

Goodarzi, Hani ^{[4
]}

Liao, Jennifer T. ^{[3
]}

O'Keeffe, Sean ^{[3
]}

Phatnani, Hemali P. ^{[3
]}

Muratet, Michael ^{[5
]}

Carroll, Michael C. ^{[1
,2
]}

Levy, Shawn ^{[5
]}

Tavazoie, Saeed ^{[3
]}

Myers, Richard M. ^{[5
]}

Maniatis, Tom ^{[3
]}

机构：

[1] Boston Childrens Hosp, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Boston, MA 02115 USA

[3] Columbia Univ, Dept Biochem & Mol Biophys, Med Ctr, New York, NY 10032 USA

[4] Rockefeller Univ, Lab Syst Canc Biol, New York, NY 10065 USA

[5] Hudson Alpha Inst Biotechnol, Huntsville, AL 35806 USA

来源：

CELL REPORTS | 2013年 / 4卷 / 02期

关键词：

MOTOR-NEURONS; SPINAL-CORD; ALTERNATIVE ACTIVATION; DISEASE PROGRESSION; NERVOUS-SYSTEM; ANIMAL-MODEL; CELLS; MUTATIONS; OSTEOPONTIN; MACROPHAGES;

D O I：

10.1016/j.celrep.2013.06.018

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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(G93A) mouse model of amyotrophic lateral sclerosis (ALS). We found that SOD1(G93A) 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 WT, 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.

引用

页码：385 / 401

页数：17

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