GEO series

MEF2C controls lysosomal and lipid clearance programs linked to Alzheimer’s disease risk in macrophages [scRNA-seq]

GSE324006 Homo sapiens (human) Single-cell RNA-seq 16 samples Submitted 2026/08/06 Platform GPL34281

At a glance

Single-cell RNA-seq · human · 16 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism: Homo sapiens (human)
Samples: 16 samples: 16 samples, each with a distinct title — no replicated groupsGroups 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: MEF2C controls lysosomal and lipid clearance programs linked to Alzheimer's disease risk in macrophagesResearch square · 2026

Summary (written by the submitters)

Risk alleles for late-onset Alzheimer’s disease (AD) are enriched in myeloid cis-regulatory elements, implicating myeloid gene-regulatory networks in disease susceptibility. A conserved lipid-associated transcriptional signature—spanning disease-associated microglia and peripheral lipid-associated macrophages (DLAM)—emerges across neurodegenerative and metabolic diseases, yet the transcriptional regulators of this gene expression program remain incompletely defined.

Read the full summary ↓

Here, we show that MEF2C—a candidate AD risk gene—is a master DLAM regulator. Using MEF2C knockout and knockdown in human iPSC-derived microglia and macrophages, we found that total or partial MEF2C loss is sufficient to induce DLAM-associated transcriptional, epigenomic, and functional remodeling, including enhanced lysosomal activity and cholesterol efflux. Integration of chromatin accessibility and regulatory epigenetic profiles with functionally informed fine-mapping linked AD causal variants in other loci to MEF2C-regulated regulatory regions and downstream risk genes. In a triculture model of AD, microglial MEF2C loss is associated with an increased DLAM population and a reduced Aβ42/40 ratio, supporting context-dependent reprogramming of microglia as a mechanism to modulate AD-relevant pathology.

Published in

MEF2C controls lysosomal and lipid clearance programs linked to Alzheimer's disease risk in macrophages

Podlesny-Drabiniok A, Kim JJ, Bezemer LJ et al. · Research square 2026 · PMID 42094058 · doi:10.21203/rs.3.rs-9164252/v1

This dataset

Open GSE324006 in finder → Find more human 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 GSE324006_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 PRJNA1432951 and SRA study SRP681372. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42094058) ↗

Study design

16 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 16 sample titles: 16 distinct titles with little repetition. 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

GSM9566607 MEF2C-KO, non-treated, differentiation 1, clone D8 (scRNA-seq)
GSM9566608 MEF2C-KO, non-treated, differentiation 1, clone G2 (scRNA-seq)
GSM9566609 MEF2C-KO, non-treated, differentiation 1, clone H11 (scRNA-seq)
GSM9566610 MEF2C-KO, non-treated, differentiation 1, clone D9 (scRNA-seq)
GSM9566611 WT, non-treated, differentiation 1, clone F2 (scRNA-seq)
GSM9566612 WT, non-treated, differentiation 1, clone C2 (scRNA-seq)
GSM9566613 WT, non-treated, differentiation 1, clone E2 (scRNA-seq)
GSM9566614 WT, non-treated, differentiation 1, clone H2 (scRNA-seq)
GSM9566615 MEF2C-KO, myelin-treated, differentiation 1, clone D8 (scRNA-seq)
GSM9566616 MEF2C-KO, myelin-treated, differentiation 1, clone G2 (scRNA-seq)
GSM9566617 MEF2C-KO, myelin-treated, differentiation 1, clone H11 (scRNA-seq)
GSM9566618 MEF2C-KO, myelin-treated, differentiation 1, clone D9 (scRNA-seq)
GSM9566619 WT, myelin-treated, differentiation 1, clone F2 (scRNA-seq)
GSM9566620 WT, myelin-treated, differentiation 1, clone C2 (scRNA-seq)
GSM9566621 WT, myelin-treated, differentiation 1, clone E2 (scRNA-seq)
GSM9566622 WT, myelin-treated, differentiation 1, clone H2 (scRNA-seq)

Datasets on a similar topic

GSE323984 MEF2C controls lysosomal and lipid clearance programs linked to Alzheimer’s disease risk in macrophages [bulkRNAseq_WTC11_iMGL] 48 samples shares mef2c, macrophages, lysosomal, clearance, alzheimer, controls, programs
GSE323982 MEF2C controls lysosomal and lipid clearance programs linked to Alzheimer’s disease risk in macrophagesm [scRNAseq_WTC11_iMGL_ReN] 16 samples shares mef2c, macrophages, lysosomal, clearance, alzheimer, controls, programs
GSE323981 MEF2C controls lysosomal and lipid clearance programs linked to Alzheimer’s disease risk in macrophages [ATAC-seq] 8 samples shares mef2c, macrophages, lysosomal, clearance, alzheimer, controls, programs
GSE263079 Microglial mechanisms drive amyloid-β clearance in immunized patients with Alzheimer’s disease [dataset3] 32 samples shares clearance, alzheimer
GSE291745 Macrophages direct location-dependent recall of B cell memory to vaccination [scRNA-seq and scVDJ-seq] 24 samples shares macrophages, scrna-seq
GSE270436 Transcriptional and epigenetic targets of MEF2C in human microglia contribute to cellular functions related to autism risk and age-related disease 21 samples shares mef2c
GSE306993 Transcriptional and epigenetic targets of MEF2C in human microglia contribute to cellular functions related to autism risk and age-related disease. 76 samples shares mef2c
GSE307817 A MEF2C transcription factor network regulates proliferation of glomerular endothelial cells in diabetic kidney disease 12 samples shares mef2c

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