Dataset Information

APOE genotype modifies the gene signature of microglial and astrocytic responses to aging

ABSTRACT: To determine how APOE genotypes impact the gene signature of microglia and astrocytes during aging at single cell level, we isolated brain cells from young (3 month of age) and aged (24 month of age) APOE2 and APOE3 and APOE4 mice, and conducted single cell RNA sequencing (scRNAseq) (4 mice/age/genotype). We annotated all the cells based on their gene markers and then focused on microglia and astrocytes for further downstream analysis. We functionally annotated each subcluster with microglia and astrocytes, based on the expression pattern of the widely accepted typical maker genes from multiple publications. Further, we identified the differentially expressed genes (DEG) in the comparison between young and aged mice for each subcluster in each APOE genotype and characterized the pathways related to these DEGs. Taken together, our dataset provided comprehensive resources to understand the APOE-regulated microglial and astrocytic responses to aging.

ORGANISM(S): Mus musculus

PROVIDER: GSE285471 | GEO | 2026/08/08

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:GFAP and vimentin deficiency alters gene expression in astrocytes and microglia in wild-type mice and changes the transcriptional response of reactive glia in mouse model for Alzheimer's disease. Reactive astrocytes with an increased expression of intermediate filament (IF) proteins Glial Fibrillary Acidic Protein (GFAP) and Vimentin (VIM) surround amyloid plaques in Alzheimer's disease (AD). The functional consequences of this upregulation are unclear. To identify molecular pathways coupled to IF regulation in reactive astrocytes, and to study the interaction with microglia, we examined WT and APPswe/PS1dE9 (AD) mice lacking either GFAP, or both VIM and GFAP, and determined the transcriptome of cortical astrocytes and microglia from 15- to 18-month-old mice. Genes involved in lysosomal degradation (including several cathepsins) and in inflammatory response (including Cxcl5, Tlr6, Tnf, Il1b) exhibited a higher AD-induced increase when GFAP, or VIM and GFAP, were absent. The expression of Aqp4 and Gja1 displayed the same pattern. The downregulation of neuronal support genes in astrocytes from AD mice was absent in GFAP/VIM null mice. In contrast, the absence of IFs did not affect the transcriptional alterations induced by AD in microglia, nor was the cortical plaque load altered. Visualizing astrocyte morphology in GFAP-eGFP mice showed no clear structural differences in GFAP/VIM null mice, but did show diminished interaction of astrocyte processes with plaques. Microglial proliferation increased similarly in all AD groups. In conclusion, absence of GFAP, or both GFAP and VIM, alters AD-induced changes in gene expression profile of astrocytes, showing a compensation of the decrease of neuronal support genes and a trend for a slightly higher inflammatory expression profile. However, this has no consequences for the development of plaque load, microglial proliferation, or microglial activation. 2 cell types from 6 conditions: cortical microglia and cortical astrocytes from 15-18 month old APPswe/PS1dE9 mice compared to wildtype littermates. Biological replicates: microglia from APPswe/PS1dE9, N=7, microglia from WT, N=7, astrocytes from APPswe/PS1dE9, N=4, microglia from WT, N=4

Dataset Information

APOE genotype modifies the gene signature of microglial and astrocytic responses to aging

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets