Single-cell nuclear architecture across cell types in the mouse brain

Diverse cell types in tissues have distinct gene expression programs, chromatin states, and nuclear architectures. To correlate such multimodal information across thousands of single cells in mouse brain tissue sections, we use integrated spatial genomics, imaging thousands of genomic loci along with RNAs and epigenetic markers simultaneously in individual cells. We reveal that cell type-specific association and scaffolding of DNA loci around nuclear bodies organize the nuclear architecture and correlate with differential expression levels in different cell types. At the submegabase level, active and inactive X chromosomes access similar domain structures in single cells despite distinct epigenetic and expression states. This work represents a major step forward in linking single-cell three-dimensional nuclear architecture, gene expression, and epigenetic modifications in a native tissue context.

Automated summary

By utilizing integrated spatial genomics, this study identified cell type-specific nuclear architecture and gene expression levels in mouse brain tissue sections, while also revealing that active and inactive X chromosomes access similar domain structures in single cells. This work represents a significant advancement in linking single-cell three-dimensional nuclear architecture, gene expression, and epigenetic modifications in a native tissue context.