The paper details the development of two-layer DNA seqFISH+, a high-resolution imaging technology designed to map the three-dimensional organization of the genome in single cells. By simultaneously analyzing over 100,000 genomic loci, the nascent transcriptome, and various subnuclear structures, researchers can observe how chromatin compartments vary across different cell types in complex tissues like the mouse cerebellum. The study reveals that active chromatin regions remain relatively consistent, while repressive regions—specifically those marked by H3K27me3 and H4K20me3—are highly cell-type specific. These repressive structures dictate radial chromosomal positioning and inter-chromosomal interactions, particularly distinguishing neurons from glial cells. Ultimately, this multi-omics approach provides a detailed view of how nuclear architecture influences gene regulation and spatial genome folding in native biological contexts.

References:

• Takei Y, Yang Y, White J, et al. Spatial multi-omics reveals cell-type-specific nuclear compartments[J]. Nature, 2025, 641(8064): 1037-1047.