Single-cell multimodal atlas reveals regulatory programs in the human brain.

A single-cell multimodal atlas of the adult human brain profiles H3K27ac and H3K27me3 across 18 regions in 750,000+ nuclei, resolving chromatin states for 500,000+ regulatory elements.

• Why it matters: Cell-type-specific regulatory programs depend on how chromatin states align with transcription, yet adult human brain epigenomic regulation has lacked direct, integrated single-cell measurements.
• What they did: The study jointly profiled transcriptomes with active or repressive histone marks across 18 adult brain regions, integrating chromatin accessibility, DNA methylation, 3D genome architecture, and spatial transcriptomes.
• The result: It linked enhancers to genes, identified regulatory programs and Polycomb-associated ultra-long-range contacts, predicts cell-type-specific effects of neurological disease variants, and shows conserved active but divergent repressive programs across species.

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