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Epigenetic heterogeneity and state-specific transcriptional programs determine differential drug response in osteosarcoma [snRNAseq + snATACseq]

GSE270504 Homo sapiens Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 4 samples Submitted 2025/09/29 Platform GPL34281
Summary
Osteosarcoma is a genomically complex tumor with structural rearrangements, aneuploidy, and chromosomal alterations, resulting in significant intertumoral heterogeneity. This complexity hampers the identification of key oncogenic pathways and subtypes. We hypothesized that chromatin accessibility could uncover molecular features to clarify their transcriptional programs, suggesting new therapies. Using ATAC-seq, H3K27ac profiling, and single-cell multiome analysis, we identified two distinct cellular states in osteosarcoma driven by unique transcription factor networks linked to normal bone development. These subtypes can be detected in patient samples via a specific gene expression signature with prognostic value.
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Direct links to NCBI, no account and no request form: the whole study as GSE270504_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1126766 and SRA study SRP515380. Searching any of these in the dataset finder brings you back here.

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