Nature study maps lifelong transcriptome of human prefrontal cortex and reveals circadian remodeling

A single-nucleus RNA sequencing study published in Nature by Yang Hui and colleagues analyzed more than 1.3 million nuclei from 284 donors in the human dorsolateral prefrontal cortex, identifying a three-stage pattern: dramatic gene-expression changes during development, stability in adulthood, and renewed change in late life. Developmental changes concentrated in neurons, involving synaptic signaling, while late-life changes were dominated by glial cells showing immune and stress reprogramming, with circadian rhythms remodeled in both neurons and glia. The study delineated ten gene-expression trajectories and linked cell-type-specific expression changes to genetic risk for schizophrenia and Alzheimer's disease.