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Gene expression profile of Fcrls+/CD11b+/Ly6C- microglia from the brain II

ABSTRACT: We used bulk RNA sequencing to investigate the molecular signature of microglia affected by microglia-specific APOE isoform (APOE3 vs. APOE4) in both WT and P301S mice

ORGANISM(S): Mus musculus

PROVIDER: GSE234391 | GEO | 2023/07/31

REPOSITORIES: GEO

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Gene expression profile of either Dead neuron+/Fcrls+/CD11b+/Ly6C- or Dead neuron-/Fcrls+/CD11b+/Ly6C- microglia from the brain II

Project description:We used bulk RNA sequencing to investigate the molecular signature of phagocytic and non-phagocytic microglia affected by APOE isoform (APOE3-KI vs. APOE3-cKO vs. APOE4-KI vs. APOE4-cKO)

2023-07-31 | GSE234350 | GEO

Gene expression profile of either Dead neuron+/Fcrls+/CD11b+/Ly6C- or Dead neuron-/Fcrls+/CD11b+/Ly6C- microglia from the brain I

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Epigenetic profile of Fcrls+/CD11b+/Ly6C- microglia from the brain

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Gene expression profile of Fcrls+/CD11b+/Ly6C- microglia from the brain V

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Project description:Apolipoprotein E (APOE) is a strong genetic risk factor for late-onset Alzheimer’s disease (AD) with APOE4 increasing and APOE2 decreasing risk relative to APOE3. In the P301S mouse model of tauopathy, ApoE4 increases tau pathology and neurodegeneration when compared to ApoE3 or the absence of ApoE. However, the role of ApoE isoforms in regulating lipid metabolism in the setting of tauopathy is unknown. Here, by using targeted lipidomics coupled with histological analysis, we demonstrate that in P301S tau mice, ApoE4 strongly promotes glial lipid accumulation along with significant perturbations in cholesterol metabolism and lysosomal function. Increasing lipid efflux in glia via administration of the LXR agonist GW3965 reduces lipid droplet accumulation in primary E4 microglia in vitro and GW3965 or Abca1 overexpression strongly attenuates tau pathology, neurodegeneration, and synapse loss in P301S/ApoE4 mice. By immunostaining, bulk and snRNA sequencing, we demonstrate reductions in reactive astrocytes and microglia as well as significant changes in cholesterol biosynthesis and metabolism in glia of tauopathy mice in response to LXR activation. These data suggest that promoting efflux of glial lipids via Abca1 could serve as a therapeutic approach to ameliorate tau and ApoE4-linked neurodegeneration.

2023-12-08 | GSE242693 | GEO

Amelioration of Tau and ApoE4-linked glial lipid accumulation and neurodegeneration with an LXR agonist

2023-12-08 | GSE242180 | GEO

Gene expression profile of either Dead neuron+/Fcrls+/CD11b+/Ly6C- or Dead neuron-/Fcrls+/CD11b+/Ly6C- microglia from the brain

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Gene expression profile of Fcrls+/CD11b+/Ly6C- microglia from the brain

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Cell-autonomous effects of APOE4 in restricting microglial response in brain homeostasis and Alzheimer’s disease

Project description:Cells in the cortex of mice expressing apoE3 or apoE4 in the microglia were isolated and subjected to the single-cell RNA seq to investigate the effects of microglia/CNS-associated macrophages (CAMs) apoE on the brain transcriptomic profiles. Our data revealed that microglia/CAM-expressed apoE3 promotes antigen presentation and immune patnways, whereas apoE4 down-regulates complement and promotes stress-related responses.

2023-11-02 | GSE241553 | GEO

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