Spatially resolved genome architecture in mouse embryonic development.

Abstract

Higher-order chromatin structure is linked to cell differentiation and aging, but its native distribution in tissues and role in organismal development remain unclear. Here, we introduce SpaceA, a spatial omics approach for in situ chromatin architecture profiling. Compared with high-throughput chromosome conformation Capture (Hi-C), SpaceA captures substantially more contacts over distances beyond 10 Mb, thereby enhancing detection of higher-order chromatin dynamics. Applied to nine mouse embryonic sections, compartment A/B identity varies spatiotemporally across native tissue environments and undergoes a dramatic shift between E12.5 and E13.5 stages, coinciding with robust transcriptional transitions but not with marked histone modification changes. Furthermore, unlike the prevalent intra-compartment interaction paradigm, the embryonic liver exhibits a distinct, enhanced chromatin condensation between compartments accompanying expression suppression, as validated by microscopy imaging and heterochromatin adhesion feature extraction. Our study establishes a platform for dissecting how tissue-spatial chromatin heterogeneity, particularly via long-range interactions, orchestrates complex biological processes in multicellular organisms.