ArticleScientific reports2025
Diffusion Smart-seq3 of breast cancer spheroids to explore spatial tumor biology and test evolutionary principles of tumor heterogeneity.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Single-cell RNA sequencing profiles drug activity within spatially engineered 3D cultures.Nature communications · 2026Article
- Article
- Metabolic starvation-induced cell swelling drives solid stress in tumors.bioRxiv : the preprint server for biology · 2026Article
- Overcoming immunotherapy resistance in triple-negative breast cancer: a critical review of mast cell plasticity, metabolic reprogramming, and organoid models.Frontiers in immunology · 2026Review
- Review
- Spatial omics in 3D culture model systems: decoding cellular positioning mechanisms and microenvironmental dynamics.Journal of translational medicine · 2025Review
- The role of 3D culture models and advanced chromatography in exosome research for triple-negative breast cancer.Journal of the Egyptian National Cancer Institute · 2025Review
- Mapping molecular landscapes in triple-negative breast cancer: insights from spatial transcriptomics.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Utility of Multicellular Spheroids for Investigating Mechanisms of Chemoresistance in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- An early-stage 3D fibroblast-featured tumor model mimics the gene expression of the naïve tumor microenvironment, including genes involved in cancer progression and drug resistance.Frontiers in oncology · 2025Article
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Authors and funding
8 authors.
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Abstract
Combining 3D cultures such as tumor spheroids and organoids with spatial omics holds great potential for tissue biology and cancer research. Yet, this potential is presently limited by technical and financial challenges of spatial omics methods and 3D cultures. To address this, we combine dye diffusion, the Smart-seq3xpress protocol for deep single-cell gene expression profiling, and dedicated probabilistic inference methods into diffusion Smart-seq3 (Smart-seq3D), to reveal the transcriptome of single cells along with their position along the core-periphery axis of spheroids. Applying Smart-seq3D to triple-negative breast tumor spheroids identifies thousands of spatial genes and reveals continuous, ungated spatial gene expression. Spatial gene and pathway expression patterns suggest biologies specific to spheroid regions, which we validate by immunostainings and pharmacological interventions. We use the Smart-seq3D data to test evolutionary principles of spatial tumor heterogeneity. Finally, we characterize aspects of tumor heterogeneity captured by 3D spheroids that are missing from 2D cultures but found in tumors in vivo. Smart-seq3D can offer a cost-efficient approach to explore how cells adapt their transcriptome to different micro-environments, reveal spatial determinants of drug resistance and could serve to characterize spatial interactions between cancer and stromal/immune cells in 3D co-cultures.
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