title: A neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model.
abstract: 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.
authors.affiliation: Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Isaac M
authors.initials: IM
authors.lastname: Chiu
authors.forename: Emiko T A
authors.initials: ET
authors.lastname: Morimoto
authors.forename: Hani
authors.initials: H
authors.lastname: Goodarzi
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Liao
authors.forename: Sean
authors.initials: S
authors.lastname: O'Keeffe
authors.forename: Hemali P
authors.initials: HP
authors.lastname: Phatnani
authors.forename: Michael
authors.initials: M
authors.lastname: Muratet
authors.forename: Michael C
authors.initials: MC
authors.lastname: Carroll
authors.forename: Shawn
authors.initials: S
authors.lastname: Levy
authors.forename: Saeed
authors.initials: S
authors.lastname: Tavazoie
authors.forename: Richard M
authors.initials: RM
authors.lastname: Myers
authors.forename: Tom
authors.initials: T
authors.lastname: Maniatis
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D059467:Transcriptome