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Mitochondrial serine metabolism fuels epigenetic remodelling in osteoclast differentiation and is the main target of methotrexate

GSE243008 Mus musculus (mouse) RNA-seq (gene expression) 58 samples Submitted 2025/09/01 Platform GPL21493
At a glance

RNA-seq (gene expression) · mouse · 58 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
58 samples: 58 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.
Summary (written by the submitters)
Osteoclasts are specialized myeloid cells with crucial roles in skeletal homeostasis and disease. Differentiation of precursor cells to osteoclasts requires extensive metabolic and epigenetic rewiring, but pathways governing these processes are poorly characterized. Here, we found that transdifferentiation into osteoclasts crucially depends on the generation of one carbon units from serine catabolized by SHMT2.
Read the full summary ↓
Serine mediatedde novopurine synthesis fuels increased mitochondrial ATP production and ultimately SAM generation necessary for epigenetic repression of macrophage lineage genes. Intriguingly, methotrexate restrains osteoclast precursors from engaging in serine mediated one carbon metabolism, unravelling a hitherto unknown therapeutic mechanism of action. Supplementation of purine precursor metabolites which restore mitochondrial ATP generation fully rescues osteoclastogenesis of SHMT2 knockout or methotrexate inhibited cells. Together, we show an essential role of serine catabolism for metabolic epigenetic coupling in osteoclast differentiation and provide a framework how methotrexate prevents osteoclast-mediated joint destruction.
This dataset
Open GSE243008 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 GSE243008_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: 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 PRJNA1015717 and SRA study SRP460022. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
58 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 58 sample titles: 58 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

+ 18 more — browse all 58 samples with per-sample file links →

Datasets on a similar topic

Search all mouse RNA-seq datasets in GEO →

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.