A neurodegeneration-specific gene expression signature and immune profile of acutely isolated microglia from an ALS mouse model

By I. Chiu, E. Morimoto, H. Goodarzi, J. Liao, S. O’Keeffe, Hemali P. Phatnani, M. Muratet, M. Carroll, S. Levy, Saeed Tavazoie and 2 more. Cell Reports, 2013

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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 SOD1G93A mouse model of ALS. We find that SOD1G93A microglia are not derived from infiltrating monocytes, and that both potentially neuroprotective and toxic factors are concurrently up-regulated, including Alzheimer’s disease genes. Mutant microglia differed from SOD1WT, LPS activated microglia, and M1/M2 macrophages, that define an ALS-specific phenotype. Concurrent mRNA/FACS analysis revealed post-transcriptional 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.

Subfields: Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/c026b5bb22996f8b3e706cf59512a73b4b35cfd8

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Citations in the corpus

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