Single-cell multiomics across nine mammals reveals cell-type-specific regulatory conservation in the brain.

Conserved and human-specific cis-regulatory elements in the mammalian brain are enriched for neuropsychiatric GWAS risk, with neurodegenerative risk linked only to conserved elements.

• Why it matters: Understanding gene regulation in the brain is crucial for elucidating the genetic basis of neurologic diseases, but the functional and evolutionary roles of cis-regulatory elements remain unclear.
• What they did: Researchers generated single-nucleus RNA- and ATAC-seq data from cortex across nine mammalian species, identified cell-type-specific candidate CREs, and used reporter assays and CRISPR interference to validate enhancer activity and function.
• The result: Findings reveal that conserved and human-specific CREs are enriched for neuropsychiatric risk, while neurodegenerative risk associates exclusively with conserved elements, advancing understanding of regulatory evolution in brain disease susceptibility.