GEO series

The Fosl1-Kdm6b Axis Controls Skeletal Muscle Fibrosis by Regulating Histone H3K27me3 [bulk RNA-seq]

GSE275140 Mus musculus (mouse) Single-nucleus RNA-seq 10 samples Submitted 2025/02/28 Platform GPL23479

At a glance

Single-nucleus RNA-seq · mouse · 10 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: 10 samples
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.

Summary (written by the submitters)

Skeletal muscle fibrosis, characterized by the replacement of functional muscle tissue with fibrotic scarring, leads to muscle function loss and potentially fatal respiratory failure, particularly in muscular dystrophy. The mechanisms driving muscle fibrosis is not yet fully understood. Our study utilized single-cell RNA-seq and single-nuclei ATAC-seq to analyze the transcriptome and chromatin accessibility of regenerating and dystrophic skeletal muscle, identifying a specific subset of fibro-adipogenic precursors (FAPs) enriched in dystrophic muscles, termed fibrotic FAPs.

Read the full summary ↓

We further demonstrated that chronic inflammation upregulates Fosl1, an early response gene, which activates the expression of Kdm6b in fibrotic FAPs. Kdm6b, a histone demethylase, specifically removes the repressive histone H3K27me3 mark. Notably, targeting Kdm6b genetically and pharmacologically inhibits fibrotic di^erentiation in human and mouse FAPs in vitro and ameliorated muscle fibrosis in mouse models in vivo. Furthermore, constitutive activation of the Fosl1-Kdm6b pathway reduced H3K27me3 modification at critical fibrotic gene loci, leading to their transcriptional activation. Taken together, our findings reveal that chronic inflammation perpetuates the Fosl1-Kdm6b axis in FAPs, causing epigenomic reprogramming and altering the H3K27me3 landscape, which is essential for preventing fibrotic di^erentiation of FAPs and skeletal muscle fibrosis.

This dataset

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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 GSE275140_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 PRJNA1149675 and SRA study SRP527293. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Samples in this study

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+ 10 more — browse all 10 samples with per-sample file links →

Datasets on a similar topic

GSE275142 The Fosl1-Kdm6b Axis Controls Skeletal Muscle Fibrosis by Regulating Histone H3K27me3 [Cut&Tag] 24 samples shares h3k27me3, fosl1-kdm6b, regulating, controls, skeletal, fibrosis, histone
GSE275143 The Fosl1-Kdm6b Axis Controls Skeletal Muscle Fibrosis by Regulating Histone H3K27me3 [HiCAR] 12 samples shares h3k27me3, fosl1-kdm6b, regulating, controls, skeletal, fibrosis, histone
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