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

Conserved and human-specific cis-regulatory elements in the brain show distinct roles in neuropsychiatric and neurodegenerative disease risk, with 9 mammalian species analyzed.

• Why it matters: Understanding gene regulation in the brain is crucial for uncovering the genetic basis of neurological diseases, but the evolution and function of regulatory elements remain poorly understood.
• What they did: Single-nucleus RNA- and ATAC-seq data from cortex across nine mammals identified cell-type-specific candidate CREs, combined with reporter assays, CRISPR validation, and a multidimensional conservation framework.
• The result: Conserved and human-specific CREs are enriched for neuropsychiatric GWAS signals, while neurodegenerative risks are linked to conserved elements, illuminating how regulatory evolution influences brain disease susceptibility.