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

Researchers examined how sex shapes gene activity throughout the human cerebral cortex at the level of individual cell types. Using single-cell RNA sequencing of cortical tissue from 30 adults (15 female, 15 male) spanning six brain regions chosen for their known sex-biased volumes, they catalogued expression differences across neurons and glial cells. The fusiform cortex, glial cells, and excitatory neurons showed the largest sex-related differences, with sex-chromosome genes contributing most strongly. Overall, more than 3,000 genes displayed sex-biased expression, and 133 of these were consistently different across multiple regions and cell types. A core set of autosomal genes connected these differences to cortical structure, hormone-regulated pathways, and genetic risk factors for brain disorders that disproportionately affect one sex. The dataset offers a detailed, cell-type-resolved reference that could help explain why neurodevelopmental, psychiatric, and neurodegenerative conditions vary in prevalence and presentation between sexes.

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An opposing molecular gradient axis underlies primate cortical organization

Researchers sought to uncover how the primate cerebral cortex is organized at the molecular level. Combining spatial transcriptomics, MRI, and retrograde tract-tracing in marmosets, they discovered two molecular gradients running in opposite directions — one originating from ancient cortical regions (allocortices) and another from primary sensory areas. These gradients, which are refined after birth, help define distinct cortical areas and align with gene expression patterns and projection pathways in the thalamus. Where the gradients intersect, regions like the default mode network show similar molecular signatures in both marmosets and humans, even where functional connectivity differs between species. Comparative analysis also revealed that marmoset and human auditory cortices are molecularly more alike to each other than to macaques, possibly linked to complex vocalization abilities. The findings suggest these opposing gradients represent a core organizing principle of primate cortical architecture.

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