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Researchers developed Spatial Hi-C-RNA, a new technology that simultaneously maps 3D genome organization and gene expression in the same tissue section at near-single-cell resolution. Applied to mouse embryos, adult mouse brains, and human melanoma samples, the method revealed that chromatin structure and gene activity create spatially coherent domains aligned with tissue architecture, with chromatin organization sometimes detecting tumor substructures invisible to gene expression analysis alone. The technology demonstrates that multiscale 3D genome features are closely linked to cell-type-specific gene expression programs across development and disease states.
Why it matters
This advancement enables scientists to understand how the physical organization of DNA in the nucleus influences gene activity within actual tissue contexts, which could improve understanding of normal development and disease processes like cancer. The ability to detect tumor subdomains through chromatin structure that are missed by standard gene expression profiling may lead to better tumor characterization and treatment strategies.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
The interplay between 3D genome architecture and transcriptional activity is fundamental to gene regulation. However, existing methodologies cannot simultaneously measure these modalities within intact tissues, limiting our understanding of how genome organization coordinates transcriptional programs across diverse cell types and spatial microenvironments. Here, we introduce Spatial Hi-C-RNA, a spatial multi-omics technology that enables the genome-wide co-mapping of chromatin conformation and transcriptome directly from the same tissue section at near-single-cell resolution. Applied to the mouse embryo and adult brains, Spatial Hi-C-RNA generated high-resolution tissue maps revealing that chromatin organization and gene expression jointly define spatially coherent domains aligned with histological structures. While concordant features were observed across modalities, distinct domain patterns also emerged, indicating that chromatin structure and transcription each contribute complementary layers of spatial regulation. We further demonstrated the robustness and biological insight of Spatial Hi-C-RNA in human melanoma, where both modalities delineated tumor boundaries and microenvironmental niches. Notably, chromatin maps revealed fine-scale tumor subdomains undetectable by transcriptomic profiling alone, highlighting the added resolution provided by spatial chromatin architecture. Integrated analysis revealed that multiscale 3D genome features, from A/B compartments and topologically associating domains to chromatin loops, are closely coupled with domain- and cell-type-specific transcriptional programs. In addition, Spatial Hi-C-RNA resolves spatiotemporal dynamics underlying embryonic lineage specification and tumor progression. Together, these capabilities extend the spatial omics landscape beyond transcriptome and epigenome profiling to the level of chromatin organization, establishing an integrative framework for understanding tissue biology across development and disease.
Source: Integrative spatial profiling of 3D genome organization and gene expression in tissue