Sex effects on gene expression across the human cerebral cortex at cell type resolution

Area of Science:

• Neuroscience
• Genomics
• Human Biology

Background:

• Sex differences in brain disorders suggest underlying biological variations.
• Sex chromosomes and hormones influence gene expression, potentially explaining these differences.

Purpose of the Study:

• To investigate sex-biased gene expression in the adult human cortex at a single-cell level.
• To identify specific genes, cell types, and brain regions exhibiting sex differences.
• To explore the link between these differences and brain disorder susceptibility.

Main Methods:

• Single-cell transcriptomic analysis of 169 adult human cortex samples (15 female, 15 male).
• Analysis across six cortical regions selected for sex-biased volumes.
• Identification of sex-biased gene expression patterns and associated genetic factors.

Main Results:

• Over 3000 genes showed sex-biased expression, with 133 consistently affected across regions and cell types.
• Strongest sex differences observed in the fusiform cortex, glia, and excitatory neurons.
• Autosomal gene signatures linked sex differences to cortical architecture, hormone regulation, and genetic risk for brain disorders.

Conclusions:

• Significant sex-specific gene expression patterns exist in the adult human brain.
• These patterns are associated with brain structure, hormonal influences, and neurological disease risk.
• Provides a foundational resource for understanding sex differences in brain function and disease.