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C9orf72 hexanucleotide repeat expansions impair microglial response in models of ALS [scRNA]

GSE302319 Homo sapiens (human) Single-cell RNA-seq 14 samples Submitted 2025/10/20 Platform GPL28038
At a glance

Single-cell RNA-seq · human · 14 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
14 samples: 7 × scRNAseq GEX human microglia vs 7 × scRNAseq HTO human microgliaGroups 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
C9orf72 hexanucleotide repeat expansions impair microglial response in ALSNature neuroscience · 2025
Summary (written by the submitters)
The involvement of microglia and neuroinflammation in amyotrophic lateral sclerosis (ALS) is well recognized, but the precise underlying molecular mechanisms remain elusive. We generated single-nuclei transcriptomic profiles from the spinal cord and motor cortex of sporadic (sALS) and C9orf72 (C9-ALS) ALS patients. We confirmed that C9orf72 is highly expressed in microglia and observed that the hexanucleotide repeat expansion (HRE) results in haploinsufficiency specifically in these cells.
Read the full summary ↓
Whereas sALS microglia transitioned towards classically defined disease-associated transcriptomic profiles, C9orf72 HRE microglia exhibited a diminished response, with alterations in phagocytic and lysosomal pathways. We confirmed these observations using a human microglia xenograft model, which showed that C9orf72 loss-of-function leads to a reduced baseline activation, with lower expression of antigen-presenting related genes. We also confirmed the alterations in the endolysosomal pathway in C9orf72-HRE and C9orf72-deficient induced pluripotent stem cell (iPSC)-derived microglia. In addition, we observed a diminished response of astrocytes in C9orf72-HRE carriers and provided an extensive map of dysregulated ligand-receptor pairs in microglia and astrocyte indicating an altered cell-cell communication in both C9orf72 and sALS. This complex cellular interplay highlights variations in the cellular substrate of sporadic and inherited forms of ALS, providing valuable insights for patient stratification and for selecting appropriate treatments.
Published in
C9orf72 hexanucleotide repeat expansions impair microglial response in ALS
Masrori P, Bijnens B, Fumagalli L et al. · Nature neuroscience 2025 · PMID 41087751 · doi:10.1038/s41593-025-02075-1
This dataset
Open GSE302319 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 GSE302319_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 PRJNA1289863 and SRA study SRP599979. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41087751) ↗
Study design
7 × scRNAseq GEX human microglia vs 7 × scRNAseq HTO human microglia

Supports a between-group comparison across 14 samples.

How we read this: 2 replicated groups read from 14 sample titles; they account for 14 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
Datasets on a similar topic

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