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Integrated single-cell profiling of RNA and DNA interactomes reveals targetable chromatin architectures in cancer [scRNA-Seq organoids]

GSE337246 Homo sapiens Expression profiling by high throughput sequencing 35 samples Submitted 2026/07/08 Platform GPL16791
Summary
The human genome is pervasively transcribed into protein-coding and regulatory non-coding RNAs whose functions are coordinated within higher-order nuclear architectures. However, direct mapping of RNA–RNA and DNA–DNA interaction networks in complex human tissues at single-cell resolution has remained a major challenge. Here, we present SCIENCE-seq, a multimodal single-cell interactomics platform enabling simultaneous detection of RNA–RNA interactions and chromatin DNA–DNA contacts within individual cells. Applied to primary glioma specimens, SCIENCE-seq reveals cancer-specific interactions organized by lncRNAs and centered on key oncogenic drivers, including EGFR, hTERT, SOX2, CDK6, CDC42, CD47, and HOX loci. These datasets uncover previously unrecognized molecular relationships between premature lncRNAs and pre-mRNAs that regulate transcription, alternative splicing, and polyadenylation. Notably, we identify a glioma-specific trans-chromosomal HOX hub driven by five interacting lncRNAs. Targeting these RNA and DNA interactions with steric antisense oligonucleotides (ASOs) or CRISPRi enables selective inhibition of oncogenic programs in malignant cells while sparing normal tissue, establishing chromatin interactomes as actionable therapeutic targets.
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Direct links to NCBI, no account and no request form: the whole study as GSE337246_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 35 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1484556 and SRA study SRP714370. Searching any of these in the dataset finder brings you back here.

Study design
5 conditions, mostly with about 7 replicates each
scRNAseq_organoids_CD47_ASO_treatment ×7 scRNAseq_organoids_CDC42_ASO_treatment ×7 scRNAseq_organoids_Control_ASO_treatment ×7 scRNAseq_organoids_LINC01116_ASO_treatment ×7 scRNAseq_organoids_SOX2_ASO_treatment ×7

Supports a between-group comparison across 35 samples.

5 replicated groups read from 35 sample titles; they account for 35 of them. Check it against the sample list below before relying on it.

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