GEO series

Molecular Drivers of Neuroinflammation in Amyotrophic Lateral Sclerosis

GSE268995 Homo sapiens (human) Single-cell RNA-seq 40 samples Submitted 2026/04/28 Platform GPL24676

At a glance

Single-cell RNA-seq · human · 40 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism: Homo sapiens (human)
Samples: 40 samples: 8 conditions, mostly with about 5 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: Integrated single-cell and spatial transcriptomic profiling in ALS uncovers peripheral-to-central immune infiltration and reprogrammingNature neuroscience · 2026

Summary (written by the submitters)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive motor neuron (MN) degeneration in the brain and spinal cord. Although neuroinflammation is increasingly recognized as a hallmark of ALS, the precise molecular programs linking immune responses to MN pathology remain poorly defined.

Read the full summary ↓

Using an integrated approach that combines single-cell and bulk RNA sequencing with spatial proteogenomics, we characterized both shared and distinct immune dynamics in peripheral blood and spinal cord tissues from sporadic ALS patients and patients carrying C9orf72 repeat expansions. Our analysis revealed broad immune remodeling in C9orf72-ALS, ALS subtype-specific and progression-associated differences in monocyte activation, and antigen-experienced CD8 effector memory T cells with clonal features consistent with antigen-driven responses. Spatial mapping revealed complement activation and lipid-programmed myeloid states converging at sites of MN loss and TDP-43 pathology. Together, these findings connect peripheral and central immune alterations to ALS heterogeneity and highlight stratified immunomodulation as a potential therapeutic strategy.

Published in

Integrated single-cell and spatial transcriptomic profiling in ALS uncovers peripheral-to-central immune infiltration and reprogramming

Zhang Z, van Olst L, Alessandrini F et al. · Nature neuroscience 2026 · PMID 42135512 · doi:10.1038/s41593-026-02300-5

This dataset

Open GSE268995 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 GSE268995_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 PRJNA1119910 and SRA study SRP511601. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42135512) ↗

Study design

8 conditions, mostly with about 5 replicates each

A ×5 B ×5 C ×5 D ×5 E ×5 F ×5 G ×5 H ×5

Supports a between-group comparison across 40 samples.

How we read this: 8 replicated groups read from 40 sample titles; they account for 40 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

GSM8304327 A1 A
GSM8304328 A2 A
GSM8304329 A3 A
GSM8304330 A4 A
GSM8304331 A5 A
GSM8304332 B1 B
GSM8304333 B2 B
GSM8304334 B3 B
GSM8304335 B4 B
GSM8304336 B5 B
GSM8304337 C1 C
GSM8304338 C2 C
GSM8304339 C3 C
GSM8304340 C4 C
GSM8304341 C5 C
GSM8304342 D1 D
GSM8304343 D2 D
GSM8304344 D3 D
GSM8304345 D4 D
GSM8304346 D5 D
GSM8304347 E1 E
GSM8304348 E2 E
GSM8304349 E3 E
GSM8304350 E4 E
GSM8304351 E5 E
GSM8304352 F1 F
GSM8304353 F2 F
GSM8304354 F3 F
GSM8304355 F4 F
GSM8304356 F5 F
GSM8304357 G1 G
GSM8304358 G2 G
GSM8304359 G3 G
GSM8304360 G4 G
GSM8304361 G5 G
GSM8304362 H1 H
GSM8304363 H2 H
GSM8304364 H3 H
GSM8304365 H4 H
GSM8304366 H5 H

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