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TGF-β signaling mediates microglial resilience to age-dependent dorsal column myelin alterations

GSE254915 Mus musculus (mouse) Single-nucleus RNA-seq 36 samples Submitted 2025/08/31 Platform GPL24247
At a glance

Single-nucleus RNA-seq · mouse · 36 samples

What it is
Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue). Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Mus musculus (mouse)
Samples
36 samples: 36 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
TGFβ signaling mediates microglial resilience to spatiotemporally restricted myelin degenerationNature neuroscience · 2026
Summary (written by the submitters)
Microglia survey and regulate central nervous system myelination during development and homeostasis. However, whether microglia-myelin interactions are anatomically regulated remains unexplored. Herein, by exploring the spinal cord, which contains several white matter tracts, we demonstrate age-dependent myelin ultrastructural abnormalities occurring in the dorsal column (DC) but not the ventral column (VC).
Read the full summary ↓
Transcriptomic analyses comparing aged and young spinal cords reveal major changes in genes regulating myelin, microglial function, and the TGF-β signaling pathway. The TGF-β signaling pathway is upregulated in the spinal cord with aging, and a TGFβ-enriched microenvironment is induced in the DC. Disrupting TGFβ1-TGFBR1/2 axis in microglia, by altering either ligand or receptor expression, leads to increased microglial activation, abnormal phagocytic behavior, and myelin loss in the DC, accompanied by neurological deficits more severe in older mice. snRNA-seq reveals a TGF-β signaling-sensitive microglial subset in the spinal cord, spatially restricted in the DC. These findings demonstrate that TGF-β signaling is indispensable for maintaining microglial resilience to myelin alterations in the DC during the aging process, highlighting a previously unresolved checkpoint mechanism of TGF-β signaling with regional specificity.
Published in
TGFβ signaling mediates microglial resilience to spatiotemporally restricted myelin degeneration
Zhu K, Liu Y, Min JH et al. · Nature neuroscience 2026 · PMID 41482590 · doi:10.1038/s41593-025-02161-4
This dataset
Open GSE254915 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 GSE254915_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 PRJNA1072623 and SRA study SRP487779. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41482590) ↗
Study design
36 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 36 sample titles: 36 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
Datasets on a similar topic

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