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MYOD1L122R induces cancer stem cell pathways to impart chemotherapy and radiation-resistance in aggressive rhabdomyosarcoma [RNA-seq_HDR]

GSE274634 Homo sapiens (human) Single-cell RNA-seq 11 samples Submitted 2026/01/14 Platform GPL30173
At a glance

Single-cell RNA-seq · human · 11 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Homo sapiens (human)
Samples
11 samples: 11 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
The PIK3CA/AKT pathway drives therapy resistance in rhabdomyosarcomaNature communications · 2025
Summary (written by the submitters)
Rhabdomyosarcoma (RMS) is a common pediatric soft tissue sarcoma of skeletal muscle. Worse outcomes are associated with specific subtypes of RMS, including the 10% of fusion-negative tumors that harbor point mutations in the DNA binding domain of MYOD1 (myogenic differentiation 1) transcription factor. Due to the rarity of these patient samples and dearth of cell lines/animal models, the molecular function of MYOD1L122R remains unknown.
Read the full summary ↓
Here, we create the first animal model of this disease showing that MYOD1L122R is not oncogenic but collaborates with RAS activation to create highly aggressive RMS in transgenic zebrafish, akin to what is reported in human disease. Limiting dilution cell transplantation revealed that MYOD1L122R also elevated the overall frequency of tumor propagating cells in the zebrafish model. We next generated isogenic knock-in MYOD1L122R human cell line models and showed that these cells were refractory to standard of care vincristine, actinomycin, and cyclophosphamide while also elevating the overall frequency of tumor propagating cells. Indeed, single-cell RNA transcriptional profiling and single-cell assay for transposase-accessible chromatin with sequencing (ATAC-Seq) of patient and patient-derived xenografts confirmed the elevation of cancer stem cell programs within MYOD1L122R tumors. Using unbiased whole-genome ChIP and RNA sequencing, we next identified the shared and differential genomic binding regions by MYOD1L122R as compared to wildtype MYOD1. Most notably, MYOD1L122R bound uniquely to and transcriptionally upregulated mesenchymal pathway enriched genes that are known to correlate with RMS cancer stemness. Finally, mechanistic studies uncovered that MYOD1L122R binds to the regulatory element of ROR2 (receptor tyrosine kinase like orphan receptor 2), upregulating its expression, which then turns on a novel WNT11-ROR2-VANGL2 axis to induce non-canonical WNT signaling and elevate cancer stemness.
Published in
The PIK3CA/AKT pathway drives therapy resistance in rhabdomyosarcoma
Yang Q, Wang Y, Corchete Sanchez LA et al. · Nature communications 2025 · PMID 41372143 · doi:10.1038/s41467-025-66632-9
This dataset
Open GSE274634 in finder → Find more human 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 GSE274634_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 PRJNA1147318 and SRA study SRP525895. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41372143) ↗
Study design
11 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 11 sample titles: 11 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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