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Single-cell multi-omics characterize colorectal tumors, adjacent healthy tissue and matched organoids identifying CRC-unique features

GSE294559 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing 72 samples Submitted 2025/07/18 Platform GPL24676
Summary
Colorectal cancer (CRC) arises in the colorectal tissue driven by genetic disorder or the accumulation of somatic mutations, leading to abnormal epithelial cell growth. In this study, we employed single-nucleus multi-omics analysis, including single-nucleus RNA-seq and single-nucleus ATAC-seq, on over 100,000 high-quality nuclei to investigate the molecular landscape of both primary tissue and patient-derived organoids (PDOs). Our analysis showed that normal PDOs (N-PDOs) derived from tissue adjacent to tumors replicate the cellular composition and differentiation trajectory of colorectal crypts. In contrast, tumor PDOs (T-PDOs) showed patient-specific transcriptomic and epigenomic heterogeneity yet consistently maintained a stem cell-like state. T-PDOs retained the somatic mutation profile of the primary tumor while also exhibiting de novo mutations not detected in either the primary tumor or N-PDOs. Notably, inferred cell-cell interaction analysis highlighted the activin signaling pathway as a potential unique feature of fibroblast-epithelial interactions within tumor microenvironment. This study provides a comprehensive view of the transition from normal to malignant colorectal epithelium and underscores the utility of PDOs as faithful model for capturing both conserved and patient-specific features of colorectal cancer.
Published in
Single-cell multi-omics characterize colorectal tumors, adjacent healthy tissue and matched (tumor) organoids identifying CRC-unique features
Yu Z, Derksen M, Te Pas BM et al. · International journal of cancer 2025 · PMID 40847690 · doi:10.1002/ijc.70103
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Direct links to NCBI, no account and no request form: the whole study as GSE294559_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 72 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1250499. Searching any of these in the dataset finder brings you back here.

Study design
40 conditions, each sampled once — no replicated groups

Supports a case/control comparison: 18 samples read as cases, 22 as controls.

Read from the first 40 of 72 sample titles: 40 distinct titles with little repetition. Check it against the sample list below before relying on it.

Samples in this study

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