title: Microglial brain region-dependent diversity and selective regional sensitivities to aging.
abstract: Microglia have critical roles in neural development, homeostasis and neuroinflammation and are increasingly implicated in age-related neurological dysfunction. Neurodegeneration often occurs in disease-specific, spatially restricted patterns, the origins of which are unknown. We performed to our knowledge the first genome-wide analysis of microglia from discrete brain regions across the adult lifespan of the mouse, and found that microglia have distinct region-dependent transcriptional identities and age in a regionally variable manner. In the young adult brain, differences in bioenergetic and immunoregulatory pathways were the major sources of heterogeneity and suggested that cerebellar and hippocampal microglia exist in a more immune-vigilant state. Immune function correlated with regional transcriptional patterns. Augmentation of the distinct cerebellar immunophenotype and a contrasting loss in distinction of the hippocampal phenotype among forebrain regions were key features during aging. Microglial diversity may enable regionally localized homeostatic functions but could also underlie region-specific sensitivities to microglial dysregulation and involvement in age-related neurodegeneration.
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, UK.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Grabert
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, UK.
authors.forename: Tom
authors.identifier: http://orcid.org/0000-0003-4749-4725
authors.initials: T
authors.lastname: Michoel
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, UK.
authors.forename: Michail H
authors.initials: MH
authors.lastname: Karavolos
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Clohisey
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, UK.
authors.forename: J Kenneth
authors.initials: JK
authors.lastname: Baillie
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, UK.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Stevens
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, UK.
authors.forename: Tom C
authors.initials: TC
authors.lastname: Freeman
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, UK.
authors.forename: Kim M
authors.initials: KM
authors.lastname: Summers
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, UK.
authors.forename: Barry W
authors.identifier: http://orcid.org/0000-0002-0521-9656
authors.initials: BW
authors.lastname: McColl
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000502:physiology*; D051379:Mice; D017628:Microglia / Q000502:physiology*; D010641:Phenotype; D059467:Transcriptome