RNA sequencing after forced turnover of adult and aged microglia
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE123847 | GEO | 2018/12/15
REPOSITORIES: GEO
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Project description:RNA sequencing after forced turnover of adult and aged microglia
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Project description:Microglia are important immune cells in the brain. Microglia undergo a series of alterations during aging and increase the susceptibility to brain dysfunctions. However, the characteristics of microglia during the aging process are not fully understood. In this study, we mapped transcriptional and epigenetic profiles of microglia from 3- to 24-month-old mice. We observed unexpected gender divergences and identified age-dependent microglia (ADEM) genes in the aging process. We then compared characteristics between microglial aging and activation. To dissect the function of aged microglia excluding the influence from other aged brain cells, we established an accelerated microglial turnover model without directly affecting other brain cells. By this model, we achieved aged microglia in non-aged brains and confirmed that aged microglia per se contribute to cognitive decline. Collectively, we provide a comprehensive resource to decode the aging process of microglia, shedding light on how microglia maintain brain functions.
2023-07-25 | GSE207948 | GEO
Project description:Microglia maintain homeostasis in the brain. However, with age, they become primed and respond more strongly to inflammatory stimuli. We show here that microglia from aged mice upregulated mammalian target of rapamycin (mTOR) complex 1 signaling regulating translation, as well as cytokine protein levels. Genetic ablation of mTOR signaling showed a dual, yet contrasting effect on microglia priming: it caused an NF-kB-dependent upregulation of priming genes at mRNA level; however, mice displayed reduced cytokine protein levels, diminished microglia activation and milder sickness behavior. The effect on translation was dependent on reduced phosphorylation of 4EBP1 and increased 4EBP1 expression, resulting in decreased binding of EIF4E to EIF4G. Similar changes were present in aged human microglia and in damage-associated microglia, indicating upregulation of mTOR-dependent translation is an essential step licensing microglia priming in ageing and neurodegeneration.
2021-07-30 | GSE156762 | GEO
Project description:During early embryogenesis microglia arise from yolk sac progenitors populating the developing CNS, where they are maintained as tissue-resident macrophages throughout the organism’s lifespan. Here, we describe an experimental system that allows the specific conditional ablation of microglia in vivo. Strikingly, we found that the microglia compartment was reconstituted within one week following depletion. Microglia repopulation relied entirely on a CNS-resident, internal pool and was independent from bone marrow-derived precursors. Newly formed microglia were found in highly proliferative, organized micro-clusters that dissolve once steady state was achieved. Gene expression profiling revealed prominent expression of Interleukin-1 (IL-1) receptor in proliferating microglia. During the repopulation phase, IL-1 signaling was neutralized by treatment with IL-1 receptor antagonist that impaired microglia proliferation. Hence, microglia harbor a highly efficient potential to restore themselves without contribution of peripheral myeloid cells. IL-1 signaling significantly participates in this restorative proliferation process and is involved in stabilizing microglia maintenance. bone marrow macrophages, wild type microglia, and repopulating microglia
2015-07-15 | E-GEOD-68376 | biostudies-arrayexpress
Project description:Changes in microglial form and function contribute to age-related cognitive impairment. Developing methods to target microglia is critical to understand and prevent the adverse effects of aging. Using a specific colony-stimulating factor 1 receptor (CSF1R) inhibitor, our lab has shown that the majority of microglia can be eliminated from the CNS (Elmore et al., 2014). Withdrawal of the CSF1R inhibitor, stimulates brain-wide repopulation with new cells, that express microglial markers (Elmore et al., 2014; Elmore et al., 2015). The impact of these newly repopulated cells on the aged brain has not been explored, but will provide useful insight into the role of microglia in aging. In addition, the therapeutic potential of replacing “primed” or “senescent” microglia in the aged brain with new cells is of great interest. Therefore, our goal was to fully characterize the gene expression profiles of the aged control vs. aged repopulated brains in comparison to young controls.
2018-10-03 | GSE94042 | GEO
Project description:Aged mice were treated intravenously (i.v) with BCG or saline to study an effect in microglia for key histone modififications H3K4me3, H3K27ac involved in trained immune response.
2024-07-24 | GSE230190 | GEO
Project description:Age-dependent alterations in microglia behavior have been implicated in neurodegeneration and CNS injuries. Here, we compared the transcriptional profiles of young versus aged microglia during stroke recovery. CD45intermediateCD11b+ microglia were FACS-isolated from the brains of young (10-week-old) and aged (18-month-old) male mice 14 days after distal middle cerebral artery occlusion (dMCAO) or sham operation and subjected to RNA-sequencing analysis. Functional groups enriched in young microglia are indicative of upregulation in cell movement, cell interactions, inflammatory responses and angiogenesis, while aged microglia exhibited a reduction or no change in these features. We confirmed reduced chemoattractive capacities of aged microglia toward ischemic brain tissue in organotypic slide co-cultures, and delayed accumulation of aged microglia around dead neurons injected into the striatum in vivo. In addition, aging is associated with an overall failure to increase the expression of microglial genes involved in cell-cell interactions, such as CXCL10. Finally, impaired upregulation of pro-angiogenic genes in aged microglia was associated with a decline in neovascularization in aged mice compared to young mice after dMCAO. This study provides a new resource to understand the mechanisms underlying microglial alterations in the aged brain milieu and sheds light on new strategies to improve microglial functions in aged stroke victims.
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Project description:Immune training in aged microglia [ChIP-seq]
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Project description:Microglial cells of the aged brain manifest signs of dysfunction that could contribute to the worst neurological outcome of stroke in the elderly. Treatment with colony-stimulating factor 1 receptor antagonists enables microglia depletion that is followed by microglia repopulation after interruption of the treatment, without any known harm to the mice. We used this strategy aiming to rejuvenate microglia function and ameliorate stroke outcome in aged mice. Cerebral ischemia/reperfusion induced strong innate immune responses in microglia highlighted by prominent type-I interferon signalling, together with cellular metabolic perturbances and lipid droplet biogenesis. Old age increased innate immune responses in microglia, which also showed more lipid droplets than microglia of young mice. Microglia renewal in old mice prevented the exaggerated type I interferon response observed in microglia after stroke, reduced the lipid droplet content, and improved the neurological outcome of stroke. This study shows that microglia renewal in old mice rejuvenates some features of old microglia and improves stroke outcome.
2022-11-29 | GSE196737 | GEO
Project description:To address whether, after depletion by Csf1r inhibition, microglia repopulating the CNS revert to a “younger” phenotype, we treated a group of 23 months old mice with the Csf1r inhibitor for 5 days and let microglia repopulate the central nervous system for 7 days. Young (3 months old) and old (23 months old) mice were included as controls. After the repopulation time, whole spinal cord samples and Fluorescence Activated Sorting (FACS)-sorted microglia cells from brain tissue were collected to perform bulk transcriptome (RNAseq) analysis. Analysis of whole spinal cord suggested that repopulating microglia tend to re-acquire its original aged phenotype. Gene expression in FACS-sorted microglia was then analyzed to better characterize its intrinsic phenotype after repopulation. In contrast to the whole spinal cord samples, old and old-treated replicates separated in Principal Component Analysis, suggesting that repopulating microglia displayed a different phenotype compared to old microglia.
2019-08-31 | GSE122085 | GEO