Integrative spatial profiling of 3D genome organization and gene expression in complex tissue

We present Spatial Hi-C-RNA, a multimodal platform that simultaneously maps genome-wide chromatin contacts and transcriptomes from the same tissue section at near single-cell resolution. Across mouse brain, developing embryos, and human melanoma, Spatial Hi-C-RNA generated multimodal maps that aligned with tissue anatomy while revealing complementary chromatin- and RNA-defined spatial patterns.

Multiscale features, including A/B compartments, topologically associating domains, and chromatin loops, were associated with region- and cell-type-specific transcriptional programs. In mouse embryos, Spatial Hi-C-RNA resolved coordinated chromatin and transcriptional remodeling during neuronal maturation across developmental stages. In human melanoma, chromatin architecture delineated intratumoral subregions not detected by RNA alone and linked tumor-state transitions to changes in compartments, domain boundaries, and regulatory programs.