title: The microglial sensome revealed by direct RNA sequencing.
abstract: Microglia, the principal neuroimmune sentinels of the brain, continuously sense changes in their environment and respond to invading pathogens, toxins and cellular debris. Microglia exhibit plasticity and can assume neurotoxic or neuroprotective priming states that determine their responses to danger. We used direct RNA sequencing, without amplification or cDNA synthesis, to determine the quantitative transcriptomes of microglia of healthy adult and aged mice. We validated our findings using fluorescence dual in situ hybridization, unbiased proteomic analysis and quantitative PCR. We found that microglia have a distinct transcriptomic signature and express a unique cluster of transcripts encoding proteins for sensing endogenous ligands and microbes that we refer to as the sensome. With aging, sensome transcripts for endogenous ligand recognition were downregulated, whereas those involved in microbe recognition and host defense were upregulated. In addition, aging was associated with an overall increase in the expression of microglial genes involved in neuroprotection.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Hickman
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Kingery
authors.forename: Toshiro K
authors.initials: TK
authors.lastname: Ohsumi
authors.forename: Mark L
authors.initials: ML
authors.lastname: Borowsky
authors.forename: Li-chong
authors.initials: LC
authors.lastname: Wang
authors.forename: Terry K
authors.initials: TK
authors.lastname: Means
authors.forename: Joseph
authors.initials: J
authors.lastname: El Khoury
mesh_terms: D000367:Age Factors; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D019295:Computational Biology; D005434:Flow Cytometry; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008024:Ligands; D017737:Macrophages, Peritoneal; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D017423:Sequence Analysis, RNA / Q000379:methods*; D059467:Transcriptome / Q000235:genetics / Q000502:physiology*
chemical_list: D039481:CD11b Antigen; D008024:Ligands; D017493:Leukocyte Common Antigens