Single-Cell Multimodal Atlas Reveals Regulatory Programs in the Human Brain

We present a large-scale single-cell multimodal atlas generated by jointly profiling transcriptome with active (H3K27ac) and repressive (H3K27me3) histone modifications across 18 brain regions. We profile >750,000 nuclei spanning 160 cell types and integrate these data with chromatin accessibility, DNA methylation, 3D genome architecture, and spatial transcriptome.

This framework annotates >500,000 regulatory elements and resolves cell-type-specific chromatin states. We link enhancers to target genes, infer gene regulatory networks, and classify chromatin interactions, revealing neuron-enriched long-range Polycomb repression of developmental genes. Integrating these maps with GWAS data and sequence-based model prioritizes noncoding variants, effector genes, and vulnerable cell types for neuropsychiatric disorders.