A lifespan transcriptomic atlas of the human prefrontal cortex at single-cell resolution.

ABSTRACT: The dorsolateral prefrontal cortex (DLPFC) underpins higher cognitive functions and is highly susceptible to age-related decline. However, a comprehensive, lifespan-resolved map of its cellular and molecular programs has been lacking. Here, we constructed the first single-nucleus transcriptomic atlas of the human DLPFC, spanning the full lifespan, profiling over 1.3 million nuclei from 284 postmortem samples ranging in age from 0-97 years. This unprecedented resource reveals three distinct transcriptomic phases: dynamic developmental remodeling, midlife stability, and late-life molecular reactivation. Non-linear modeling of age trends uncovers ten distinct trajectories, including a neuronal resilience program peaking in early adolescence and glial aging programs marked by immune activation

SUBMITTER: Yang H 

PROVIDER: S-EPMC12632665 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature