GEO series

ApoE4 Drives Microglial Lipid Dysregulation in Alzheimer’s Disease via Epigenetic Reprogramming of the AsxL1/LXRα–H3K4me3 Axis

GSE319246 Mus musculus (mouse) Single-nucleus RNA-seq 24 samples Submitted 2026/02/16 Platform GPL24247

At a glance

Single-nucleus RNA-seq · mouse · 24 samples

What it is: Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue). Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
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: ApoE4 Drives Microglial Lipid Dysregulation in Alzheimer's Disease via Epigenetic Reprogramming of the Asxl1/LXRα-H3K4me3 AxisJournal of neuroinflammation · 2026

Summary (written by the submitters)

Background The ε 4 allele of apolipoprotein E gene (ApoE) stands as the greatest genetic risk factor for late-onset Alzheimer’s disease (AD). Although microglia accumulating lipid droplets (LDAM) have been implicated in AD pathogenesis, the mechanistic link between ApoE4 and microglial lipid dysregulation remains elusive. Methods We employed a multi-omics approach, combining snRNA-seq and locus-specific epigenetic analysis, alongside microglia-specific gene manipulation in ApoE-targeted replacement (TR) mice.

Read the full summary ↓

Primary microglia were challenged with cholesterol to simulate lipid overload conditions. Results In mid-life ApoE4-TR mice, microglia within the dentate gyrus developed pronounced lipid droplet accumulation, concurrent with impaired Aβ clearance and a pro-inflammatory shift. snRNA-seq unveiled a unique microglial cluster in ApoE4 mice, enriched for lipid-metabolism genes and marked by the pronounced downregulation of the hub gene AsxL1. Mechanistically, ApoE4 attenuated the AsxL1–LXRα interaction, leading to reduced H3K4me3 occupancy at promoters of lipid-efflux genes such as Abca1. Crucially, CRISPR-mediated, microglia-specific overexpression of AsxL1 restored H3K4me3 levels, normalized cholesterol efflux, and rescued Aβ phagocytic deficits in vivo. Conclusions Our findings define an epigenetic pathway whereby ApoE4 drives microglial dysfunction via the AsxL1–LXRα–H3K4me3 axis, fostering the LDAM phenotype. Enhancing AsxL1 function presents a promising therapeutic avenue for countering ApoE4-mediated pathogenesis in AD.

Published in

ApoE4 Drives Microglial Lipid Dysregulation in Alzheimer's Disease via Epigenetic Reprogramming of the Asxl1/LXRα-H3K4me3 Axis

Lin L, Pan Z, Wei Z et al. · Journal of neuroinflammation 2026 · PMID 41808104 · doi:10.1186/s12974-026-03740-3

This dataset

Open GSE319246 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 GSE319246_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1422681 and SRA study SRP676504. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41808104) ↗

Study design

6 conditions, mostly with about 4 replicates each

RNA-seq of mus brain in January, biol ×4 RNA-seq of mus brain in February, biol ×4 RNA-seq of mus brain in March, biol ×4 RNA-seq of mus brain in April, biol ×4 RNA-seq of mus brain in May, biol ×4 RNA-seq of mus brain in June, biol ×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

GSM9514236 RNA-seq of mus brain in January, biol repl1 RNA-seq of mus brain in…
GSM9514237 RNA-seq of mus brain in January, biol repl2 RNA-seq of mus brain in…
GSM9514238 RNA-seq of mus brain in January, biol repl3 RNA-seq of mus brain in…
GSM9514239 RNA-seq of mus brain in January, biol repl4 RNA-seq of mus brain in…
GSM9514240 RNA-seq of mus brain in February, biol repl1 RNA-seq of mus brain in…
GSM9514241 RNA-seq of mus brain in February, biol repl2 RNA-seq of mus brain in…
GSM9514242 RNA-seq of mus brain in February, biol repl3 RNA-seq of mus brain in…
GSM9514243 RNA-seq of mus brain in February, biol repl4 RNA-seq of mus brain in…
GSM9514244 RNA-seq of mus brain in March, biol repl1 RNA-seq of mus brain in…
GSM9514245 RNA-seq of mus brain in March, biol repl2 RNA-seq of mus brain in…
GSM9514246 RNA-seq of mus brain in March, biol repl3 RNA-seq of mus brain in…
GSM9514247 RNA-seq of mus brain in March, biol repl4 RNA-seq of mus brain in…
GSM9514248 RNA-seq of mus brain in April, biol repl1 RNA-seq of mus brain in…
GSM9514249 RNA-seq of mus brain in April, biol repl2 RNA-seq of mus brain in…
GSM9514250 RNA-seq of mus brain in April, biol repl3 RNA-seq of mus brain in…
GSM9514251 RNA-seq of mus brain in April, biol repl4 RNA-seq of mus brain in…
GSM9514252 RNA-seq of mus brain in May, biol repl1 RNA-seq of mus brain in…
GSM9514253 RNA-seq of mus brain in May, biol repl2 RNA-seq of mus brain in…
GSM9514254 RNA-seq of mus brain in May, biol repl3 RNA-seq of mus brain in…
GSM9514255 RNA-seq of mus brain in May, biol repl4 RNA-seq of mus brain in…
GSM9514256 RNA-seq of mus brain in June, biol repl1 RNA-seq of mus brain in…
GSM9514257 RNA-seq of mus brain in June, biol repl2 RNA-seq of mus brain in…
GSM9514258 RNA-seq of mus brain in June, biol repl3 RNA-seq of mus brain in…
GSM9514259 RNA-seq of mus brain in June, biol repl4 RNA-seq of mus brain in…

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.