Common variation of cell abundances and gene expression in the human striatum.

Single-nucleus RNA-seq of 3.9 million nuclei from 178 adult donors shows that astrocytes, microglia, and OPC abundance varies across individuals and is linked to age-related shifts and gene-expression patterns in striatum and prefrontal cortex.

• Why it matters: Inter-individual cellular and molecular differences in the human brain remain unclear, especially outside the neocortex, limiting understanding of brain variation and potential vulnerabilities.
• What they did: The study performed snRNA-seq on 3.9 million nuclei from 178 adult brain donors, quantifying cell-type abundances and cell-type–specific age and genotype effects, and predicting donor age from RNA-expression patterns (median absolute error 6.6 years).
• The result: OPC proportions declined by 40% from ages 30–80 in cortex and striatum, age-linked gene-expression changes varied by cell type, and common variants were associated with expression of nearly 10,000 genes, mostly in a cell-type–specific manner distinguishing striatal from cortical neurons.

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