The 3D architecture of genome serves as a fundamental matrix orchestrating global gene expression. However, its organization in multicellular organisms, particularly for 1-100 Mb scale architecture, remains elusive. Here, we introduce SpaceA, a spatial omics approach for assessing genome architecture in-situ in tissue sections. Applied to mouse embryo, SpaceA effectively captured a high number of DNA contacts over distances greater than 10Mb, profiling chromatin compartment formations and interactions within native cellular environments. Specifically, compartment strength analysis revealed that enhanced DNA interactions within each compartment B were linked to weakened interactions among multiple compartments A, and an increase in closed-compartment interactions was associated with a decrease in remote-compartment interactions. These findings suggest novel chromatin-packing mechanisms in native environments, potentially impacting global gene expression and tissue development. Our study underscores the utility of SpaceA in exploring the spatial heterogeneity of genome architecting in multicellular organisms.

Spatial Omic; Genome Architecture; Native Cellular Environment; Compartment Organization; Embryo