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Immune checkpoint LAG-3 governs stage-dependent and disease-associated microglial modules in ALS model mice

GSE320562 Mus musculus (mouse) RNA-seq (gene expression) 32 samples Submitted 2026/07/15 Platform GPL34290
At a glance

RNA-seq (gene expression) · mouse · 32 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
32 samples: 9 conditions, mostly in triplicateGroups 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
Immune checkpoint LAG-3 governs stage-dependent and disease-associated microglial modules in ALS model miceJournal of neuroinflammation · 2026
Summary (written by the submitters)
Immune checkpoint molecules, inhibitory receptors originally characterized in T cell biology, have recently emerged as regulators of microglial function in neurodegeneration, yet their roles in amyotrophic lateral sclerosis (ALS) remain unexplored. Here, we investigated LAG-3, an inhibitory immune checkpoint receptor, in microglial regulation during ALS pathogenesis using SOD1G93A mice.
Read the full summary ↓
LAG-3 expression was progressively upregulated in spinal cord microglia during disease progression, and LAG-3-high microglia exhibited a disease-associated microglia (DAM) transcriptional signature. Genetic deletion of LAG-3 produced a biphasic phenotype, with accelerated disease onset but significantly prolonged disease duration. LAG-3 deficiency enhanced inflammatory microglial responses at the early disease stage, whereas at the late stage it suppressed inflammatory signaling while selectively preserving phagocytic effector gene expression, demonstrating that LAG-3 dissociates the inflammatory and phagocytic modules within the DAM program in a stage-dependent manner. These transcriptional changes translated into enhanced phagocytic capacity in primary microglia and were accompanied by amelioration of the spinal cord environment, reflected by suppression of inflammatory pathways and restoration of oxidative phosphorylation. Our findings identify LAG-3 as a stage-dependent regulator of microglial functional states in ALS and support the concept that immune checkpoint molecules constitute a class of module-level regulators of microglial function in neurodegeneration.
Published in
Immune checkpoint LAG-3 governs stage-dependent and disease-associated microglial modules in ALS model mice
Morisaki Y, Nomura N, Ohshima M et al. · Journal of neuroinflammation 2026 · PMID 42343420 · doi:10.1186/s12974-026-03919-8
This dataset
Open GSE320562 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 GSE320562_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 PRJNA1428823 and SRA study SRP679583. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42343420) ↗
Study design
9 conditions, mostly in triplicate
LAG-3-Low_G93A_microglia ×5 LAG-3-High_G93A_microglia ×5 WT_microglia ×4 P120_G93A ×3 P140_G93A ×3 P120_G93AKO ×3 P140_G93AKO ×3 G93A_140d_spinalcord ×3 +1 more

Supports a between-group comparison across 32 samples.

How we read this: 9 replicated groups read from 32 sample titles; they account for 32 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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