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Exploring the sex and estrous cycle-dependent differences in microglia response to amyloid-beta pathology in female and male C57BL6/J (WT) and 5xFAD using bulk mRNAseq of isolated microglia.

GSE306854 Mus musculus (mouse) RNA-seq (gene expression) 24 samples Submitted 2026/01/08 Platform GPL34290
At a glance

RNA-seq (gene expression) · mouse · 24 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
24 samples: 6 conditions, mostly with about 4 replicates eachGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Microglial interferon signaling and Aβ plaque pathology are enhanced in female 5xFAD Alzheimer's disease mice, independent of estrous cycle stageJournal of neuroinflammation · 2025
Summary (written by the submitters)
Alzheimer’s disease (AD) presents with a sex bias where women are at higher risk and exhibit worse cognitive decline and brain atrophy compared to men. Microglia play a significant role in the pathogenesis and progression of AD and have been shown to be sexually differentiated in health and disease. Whether and how microglia contribute to the sex differences in AD remains to be elucidated.
Read the full summary ↓
Herein, we characterize the sex differences in microglial transcriptomic changes that occur in females and males in response to amyloid-beta (Aβ). In females, we focus on two hormonally distinct stages of the rodent estrous cycle: proestrus and diestrus. Our transcriptomic data revealed that female microglia are not overtly different at the proestrus or diestrus stages. However, we found stark sex differences between female and male microglia transcriptomes in the 5xFAD brains, where female 5xFAD microglia upregulated genes involved in glycolytic metabolism, antigen presentation, disease-associated microglia, and microglia neurodegenerative phenotype (DAM/MGnD) compared to male 5xFAD microglia. Interestingly, a significant proportion of differentially expressed genes (DEGs) between female and male 5xFAD microglia were interferon-stimulated genes (ISGs), all of which were upregulated in females.
Published in
Microglial interferon signaling and Aβ plaque pathology are enhanced in female 5xFAD Alzheimer's disease mice, independent of estrous cycle stage
Calcines-Rodríguez L, Noyes-Martel N, Becker JL et al. · Journal of neuroinflammation 2025 · PMID 41455993 · doi:10.1186/s12974-025-03659-1
This dataset
Open GSE306854 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE306854_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1312530 and SRA study SRP614709. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41455993) ↗
Study design
6 conditions, mostly with about 4 replicates each
Pro-BL6 ×4 Die-5xFAD ×4 Die-BL6 ×4 Males-BL6 ×4 Pro-5xFAD ×4 Males-5xFAD ×4

Supports a between-group comparison across 24 samples.

How we read this: 6 replicated groups read from 24 sample titles; they account for 24 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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