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Series GSE233400 Query DataSets for GSE233400
Status Public on Aug 18, 2023
Title Microglial senescence contributes to female-biased neuroinflammation in the aging mouse hippocampus: implications for Alzheimer’s disease
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Microglia, the brain’s principal immune cells, have been implicated in the pathogenesis of Alzheimer’s disease (AD), a condition shown to affect more females than males. Although sex differences in microglial function and transcriptomic programming have been described across development and in disease models of AD, no studies have comprehensively identified the sex divergences that emerge in the aging mouse hippocampus. Further, existing models of AD generally develop pathology (amyloid plaques and tau tangles) early in life and fail to recapitulate the aged brain environment associated with late-onset AD. Here, we examined and compared the transcriptomic and translatomic sex effects in young and old murine hippocampal microglia. Hippocampal tissue from C57BL6/N and microglial NuTRAP mice of both sexes were collected at young (5-6 month-old [mo]) and old (22-25 mo) ages. Cell sorting and affinity purification techniques were used to isolate the microglial transcriptome and translatome for RNA-sequencing and differential expression analyses. Flow cytometry, qPCR, and imaging approaches were used to confirm the transcriptomic findings. There were marginal sex differences identified in the young hippocampal microglia, with most differentially expressed genes (DEGs) restricted to the sex chromosomes. Both sex chromosomally- and autosomally-encoded sex differences emerged with aging. These sex DEGs identified at old age were primarily female-biased and enriched in senescent and disease-associated microglial signatures. Pathway analyses identified upstream regulators induced to a greater extent in females than in males, including inflammatory mediators IFNG, TNF, and IL1B, as well as AD-risk genes TREM2 and APP. These data suggest that female microglia adopt disease-associated and senescent phenotypes in the aging mouse hippocampus, even in the absence of disease pathology, to a greater extent than males. This sexually divergent microglial phenotype may explain the difference in susceptibility and disease progression in the case of AD pathology. Future studies will need to explore sex differences in microglial heterogeneity in response to AD pathology and determine how sex-specific regulators (i.e., sex chromosomal or hormonal) elicit these sex effects.
 
Overall design Comparative gene expression profiling analysis of RNA-seq data for transcriptome (CD11b-MACS) and translatome (Cx3cr1-TRAP) from hippocampal microglia isolated from young and old mice
 
Contributor(s) Ocañas SR, Pham KD, Cox JE, Keck AW, Ko S, Ampadu FA, Porter HL, Ansere VA, Kulpa A, Kellogg CM, Machalinski AH, Chucair-Elliott AJ, Freeman WM
Citation(s) 37587511, 38058312
Submission date May 25, 2023
Last update date Dec 14, 2023
Contact name Michael Stout
E-mail(s) [email protected]
Organization name Oklahoma Medical Research Foundation
Department Aging and Metabolism
Street address 825 N.E. 13th Street
City Oklahoma City
State/province OK
ZIP/Postal code 73104
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (38)
GSM7426813 YF1
GSM7426814 YF3
GSM7426815 YF4
Relations
BioProject PRJNA976199

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Supplementary file Size Download File type/resource
GSE233400_CD11b_cpm_081722.xlsx 2.2 Mb (ftp)(http) XLSX
GSE233400_Cx3cr1_cpm_081722.xlsx 3.5 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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