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Single cell RNA sequencing of spinal motor neurons and interneurons differentiated from isogenic FUS and TARDBP human induced pluripotent stem cell lines harbouring ALS-causative mutations

GSE226482 Homo sapiens (human) Single-cell RNA-seq 1415 samples Submitted 2025/04/30 Platform GPL16791Platform GPL24676
At a glance

Single-cell RNA-seq · human · 1415 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
1415 samples: 8 conditions, mostly with about 92 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
Single-cell RNA-sequencing reveals early mitochondrial dysfunction unique to motor neurons shared across FUS- and TARDBP-ALSNature communications · 2025
Summary (written by the submitters)
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease that can be inherited with genetic mutations in > 25 different genes including e.g. FUS, TARDBP, and C9ORF72. It is currently unclear how these mutations lead to motor neuron degeneration and whether different gene mutations converge on similar pathogenic pathways early on, or if each mutation leads to motor neuron death in a unique manner.
Read the full summary ↓
To address these questions in depth, we generated a number of isogenic iPSC (induced pluripotent stem cell) lines harbouring point mutations in FUS (R495X and P525L) or TARDBP (M337V) as well as a knock-out of FUS (FUS-KO), to discern loss-versus gain-of-function mechanisms in FUS. The use of isogenic lines enables identification of subtle early disturbances in the transcriptome which may be detrimental but impossible to detect when lines of different backgrounds are used. We conducted single cell RNA sequencing of motor neurons and interneurons derived from these lines using Smart-seq2. We show that ALS-causative mutations elicit a much larger transcriptional response in motor neurons than in interneurons. A large number of transcripts were coregulated across FUS R495X and P525L motor neurons and the majority of these were part of gain-of-function of FUS. Cross-comparison with isogenic ALS-linked TARDBP M337V identified an early dysfunctions shared across ALS-causative mutations unique to motor neurons that could have major implications for motor neuron survival and that might be targeted therapeutically.
Published in
Single-cell RNA-sequencing reveals early mitochondrial dysfunction unique to motor neurons shared across FUS- and TARDBP-ALS
Schweingruber C, Nijssen J, Mechtersheimer J et al. · Nature communications 2025 · PMID 40389397 · doi:10.1038/s41467-025-59679-1
This dataset
Open GSE226482 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 GSE226482_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 PRJNA940433 and SRA study SRP425343. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40389397) ↗
Study design
8 conditions, mostly with about 92 replicates each
Diff_D2_Protocol_P1_Line_DF6-9-9T.B_Control_C… ×92 Diff_D3_Protocol_P1_Line_DF6-9-9T.B_Control_C… ×72 Diff_D2_Protocol_P1_Line_DF6-9-9T.B_FUS_KO_Ce… ×61 Diff_D2_Protocol_P1_Line_DF6-9-9T.B_FUS_R495X… ×48 Diff_D2_Protocol_P1_Line_DF6-9-9T.B_FUS_P525L… ×40 Diff_D2_Protocol_P1_Line_DF6-9-9T.B_TARDBP_M3… ×38 Diff_D4_Protocol_P2_Line_DF6-9-9T.B_FUS_KO_Ce… ×32 Diff_D4_Protocol_P2_Line_DF6-9-9T.B_Control_C… ×17

Supports a between-group comparison across 400 samples.

How we read this: 8 replicated groups read from the first 400 of 1415 sample titles; they account for 400 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

+ 1375 more — browse all 1415 samples with per-sample file links →

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