Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Microglial repopulation rewires and rejuvenates the aged brain

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE94042 | GEO | 2018/10/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gene expression profile at single-cell level of microglia from 3-, 14- and 24-month-old female mouse brains

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 | GSE207932 | GEO

Bulk RNA-seq of microglia at different ages

2023-07-25 | GSE208386 | GEO

ATAC-seq of microglia from 3-, 14- and 24-month-old female mouse brains treated by LPS or PBS

2023-07-25 | GSE208346 | GEO

scRNA-seq of brain cells from 3- and 24-month-old mouse brains

2023-07-25 | GSE208292 | GEO

Gene expression profile at single cell level of microglia from forced microglia turnover and control mouse brain

2023-07-25 | GSE207948 | GEO

SIRT1 deficiency in microglia contributes to cognitive decline in aging and neurodegeneration via epigenetic regulation of IL-1beta

Project description:Aging is the predominant risk factor for neurodegenerative diseases. One key phenotype as brain ages is the aberrant innate immune response characterized by proinflammation. However, the molecular mechanisms underlying aging-associated proinflammation are poorly defined. Whether chronic inflammation plays a causal role in cognitive decline in aging and neurodegeneration has not been established. Here we established a mechanistic link between chronic inflammation and aging microglia, and demonstrated a causal role of aging microglia in neurodegenerative cognitive deficits. Expression of microglial SIRT1 reduces with the aging of microglia. Genetic reduction of microglial SIRT1 elevates IL-1Î² selectively, and exacerbates cognitive deficits in aging and in transgenic mouse models of frontotemporal dementia (FTD). Interestingly, the selective activation of IL-1Î² transcription by SIRT1 deficiency is likely mediated through hypomethylating the proximal promoter of IL-1Î². Consistent with our findings in mice, selective hypomethylation of IL-1Î² at two CpG sites are found in normal aging humans and demented patients with tauopathy. Our findings reveal a novel epigenetic mechanism in aging microglia that contributes to cognitive deficits in neurodegenerative diseases. Study of changes related to alterations of SIRT1 levels in microglia of young and aged animals and in models of neurodegenerative dementia

2014-10-01 | E-GEOD-56452 | biostudies-arrayexpress

scRNA-seq of brain cells from control and 3xDR mouse brains

Project description:As important immune cells, microglia undergo a series of alterations during aging that increase the susceptibility to brain dysfunctions. However, the longitudinal characteristics of microglia remain elusive. In this study, we mapped the transcriptional and epigenetic profiles of microglia from 3- to 24-month-old mice. We observed unexpected sex differences and identified age-dependent microglia (ADEM) genes during the aging process. We then compared the characteristics of aging and reactivity in female microglia at the single-cell resolution and epigenetic level. To dissect the functions 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, our work provides a comprehensive resource for decoding the aging process of microglia, shedding light on how microglia maintain brain functions.

2023-07-25 | GSE226286 | GEO

The microglial response to inhibition of Colony-Stimulating-Factor-1 Receptor by PLX3397 differs by sex in adult mice

Project description:Microglia, the resident macrophage of the brain, are derived from the yolk sac and colonize the brain before the blood-brain barrier forms. Once established, they expand locally and require Colony-stimulating factor 1 receptor (CSF1R) signaling for their development and maintenance. CSF1R inhibitors have been used extensively to deplete microglia in the healthy and diseased brain. In this study, we demonstrated sex-dependent differences in the microglial response to the CSF1R inhibitor PLX3397. Male mice exhibited greater microglial depletion compared to females. Transcriptomic and flow cytometry analysis revealed sex-specific differences in the remaining microglia population, with female microglia upregulating autophagy and proteostasis pathways while male microglia increased mitobiogenesis. Furthermore, manipulating key microglial receptors by using different transgenic mouse lines resulted in changes in depletion efficacies that were also sex-dependent. These findings suggest sex-dependent microglial survival mechanisms, which might contribute to the well-documented sex differences in various neurological disorders.

2024-10-06 | GSE278897 | GEO

single-cell RNA-seq profile of adult microglia under acute Csf1r inhibition and early repopulation

Project description:Microglia are the resident myeloid cell in the central nervous system (CNS). Like other terminally differentiated myeloid cells, microglia rely on Csf1r signaling for survival and maintenance. Surprisingly, a small subset of microglia in the murine brain can survive without Csf1r signaling, as shown in Csf1r KO mice as well as in mice that have been treated with Csf1r inhibitor PLX5622. The nature of such Csf1r independent microglial population has not been fully characterized. Here we applied single-cell RNA-seq to examine the remaining microglia in C57/BL6J mice that were treated with PLX5622 diet (1200 mg/kg, 14 days), which results >90% microglial removal.

2019-12-01 | GSE133773 | GEO

single-cell RNA-seq profile of microglia under acute Csf1r inhibition and early repopulation in adult brain

2020-05-09 | GSE150169 | GEO