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 donor age predicts RNA-expression patterns with a median absolute error of 6.6 years across cell types 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 vulnerability.
• What they did: The study profiled striatum and prefrontal cortex using single-nucleus RNA-seq, quantified cell-type abundances, tested age-linked expression by cell type, and used RNA-expression patterns to predict donor age.
• The result: OPC proportions declined by 40% from ages 30–80 in cortex and striatum, age-associated expression changes varied by cell type, and common variants linked to expression of nearly 10,000 genes were largely cell-type-specific, distinguishing striatal from cortical neurons.

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