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Aged muscle stem cells epigenetically drive the expansion of mesenchymal progenitors [bulk RNA-Seq]

GSE282285 Mus musculus (mouse) RNA-seq (gene expression) 31 samples Submitted 2025/08/22 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 31 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
31 samples: 10 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
Epigenetic dysregulation in aged muscle stem cells drives mesenchymal progenitor expansion via IL-6 and Spp1 signalingNature aging · 2025
Summary (written by the submitters)
Sarcopenia, the age-related loss of muscle mass and strength, is characterized by impaired muscle repair and increased deposition of fibrotic tissue. Yet, the specific role of individual cell types in the development of fibrosis remains poorly defined. Here, we report that aged muscle stem cells (MuSCs) directly instruct fibro-adipogenic progenitors (FAPs) to proliferate and adopt a fibrogenic phenotype.
Read the full summary ↓
Polycomb Ezh2-/- or aged mice exhibited regenerative defects, FAP expansion, fibrosis, and elevated levels of MuSC-secreted interleukin 6 (IL-6) and Spp1/Osteopontin. In aged MuSCs, H3K27me3 erosion at the NF-kB gene correlated with increased expression and enhanced chromatin recruitment at the IL-6 and Spp1 genes, leading to their activation. Blocking IL-6 and Spp1 signaling in co-cultures of aged MuSC and FAPs, or aged mice, reduced FAP proliferation and muscle fibrosis. In summary, our results indicate that aged MuSCs instruct FAPs to proliferate and acquire a fibrogenic phenotype through a mechanism involving epigenetically-mediated derepression of NF-kB and increased activation of IL-6 and Spp1- both of which are potential pharmacological targets.
Published in
Epigenetic dysregulation in aged muscle stem cells drives mesenchymal progenitor expansion via IL-6 and Spp1 signaling
Riparini G, Mackenzie M, Naz F et al. · Nature aging 2025 · PMID 41162675 · doi:10.1038/s43587-025-01002-0
This dataset
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.

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 GSE282285_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1188066 and SRA study SRP546161. Searching any of these in the dataset finder brings you back here.

Study design
10 conditions, mostly in triplicate
MuSC_Ctrl_3dpi ×4 FAP_Ctrl_3dpi ×4 FAP_iEzh2KO_3dpi ×4 MuSC_iEzh2KO_3dpi ×3 MuSC_Ctrl_7dpi ×3 MuSC_iEzh2KO_7dpi ×3 MuSC_Ctrl_quiescent ×3 MuSC_iEzh2KO_quiescent ×3 +2 more

Supports a between-group comparison across 31 samples.

How we read this: 10 replicated groups read from 31 sample titles; they account for 31 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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