LAUSR

Description Nuclear organization in the brain The brain consists of different cell types, neurons and glial cells, that have different nuclear architecture. Takei et al. used multiplexed imaging tools to examine the spatial arrangement of more than 3000 DNA loci, along with epigenetic marks and gene expression patterns, simultaneously in the same single cells in mouse brain cortex. They observed features that are conserved across cell types, as well as cell-type-dependent spatial arrangements at the megabase level. At the level of tens of kilobases, they observed similar single-cell chromosome domain conformations in both active and inactive X chromosomes that are averaged out in population-based measurements. —DJ Multimodal measurements in single cells in the brain reveal nuclear organization principles across cell types. 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.