Sex effects on gene expression across the human cerebral cortex at cell type resolution
Summary
Sex differences in neurodevelopmental, psychiatric, and neurodegenerative disease susceptibility may arise from sex chromosome and hormonal influences on cell type-specific gene expression. We present a single-cell transcriptomic analysis of adult human cortex performed using 169 samples from 15 females and 15 males (age 26 to 78 years) across six regions selected according to their sex-biased volumes. Sex-based analysis identified the strongest differences in the fusiform cortex, glia, an
Content
# Sex effects on gene expression across the human cerebral cortex at cell type resolution
*Published: 2026 Apr 16*
Sex differences in neurodevelopmental, psychiatric, and neurodegenerative
disease susceptibility may arise from sex chromosome and hormonal influences on
cell type-specific gene expression. We present a single-cell transcriptomic
analysis of adult human cortex performed using 169 samples from 15 females and
15 males (age 26 to 78 years) across six regions selected according to their
sex-biased volumes. Sex-based analysis identified the strongest differences in
the fusiform cortex, glia, and excitatory neurons and among sex-chromosome
genes. More than 3000 genes showed sex-biased expression, including 133 with
consistent effects across regions and cell types. Core autosomal signatures
linked sex differences to cortical architecture, hormone-responsive regulation,
and genetic risk for sex-biased brain disorders. This study advances our
understanding of sex differences in human brains and provides a valuable
resource to support future research.
DOI: 10.1126/science.aea9063