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Epitranscriptomic program promotes skeletal stem cell quiescence and pluripotency by regulating proteostasis via METTL3-FEM1B-GLI1 axis

GSE284224 Mus musculus (mouse) RNA-seq (gene expression) 44 samples Submitted 2024/12/18 Platform GPL21273
At a glance

RNA-seq (gene expression) · mouse · 44 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
44 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.
Paper
An epitranscriptomic program maintains skeletal stem cell quiescence via a METTL3-FEM1B-GLI1 axisThe EMBO journal · 2025
Summary (written by the submitters)
Skeletal stem cells (SSCs) maintain the hierarchy of skeletal system via pluripotency and differentiation capacity. However, it remains largely unknown how these cells adapt its highly nutrient-deficient niche and precisely regulate their function to keep this skeletal hierarchical organization. Here, we delineate a comprehensive m6A landscape across skeletal hierarchy, and identify a new epitranscriptomic program to promote SSCs quiescence and potency by regulating proteostasis via METTL3-FEM1B-GLI1 axis.
Read the full summary ↓
We find m6A modifications arise mostly from skeletal stem cells (SSCs) in stem-progenitor population and play critical roles in cell fate maintenance and transformation in skeletal hierarchy. Genetic deletion of Mettl3 in skeletal stem and progenitors impairs bone development with shortened limbs, disturbs growth plate, and decreases bone mass. Moreover, Mettl3 loss induces quiescence loss, and damages the self-renewal ability, and differentiation ability of SSCs. Mechanistically, Mettl3-mediated m6A modification reduces mRNA stability of a Cul2-RING E3 ligase complex substrate-recognition subunit Fem1b, which subsequently influences proteostasis of SSCs and stabilizes Gli1 protein, a key transcription factor of Hedgehog pathway for maintaining SSC identity and function. Thus, our findings present a fascinating portrait of m6A modification of skeletal hierarchy and reveal the essential role of an epitranscriptome-proteostasis axis in maintaining SSC function.
Published in
An epitranscriptomic program maintains skeletal stem cell quiescence via a METTL3-FEM1B-GLI1 axis
Wang J, Liu W, Zhang T et al. · The EMBO journal 2025 · PMID 40016417 · doi:10.1038/s44318-025-00399-z
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 GSE284224_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 PRJNA1198024 and SRA study SRP551322. Searching any of these in the dataset finder brings you back here.

Samples in this study

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+ 44 more — browse all 44 samples with per-sample file links →

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