Bulk and single-cell RNA-seq analyses characterize a DBP-related circadian signature in ischemic stroke
TL;DR
These findings establish circadian gene-based patient stratification and implicate microglial DBP as a modulator of post-stroke injury, offering potential avenues for risk assessment and targeted intervention.
Abstract
Summary Circadian rhythm disruption is associated with ischemic stroke outcomes, yet the roles of circadian genes in stroke pathology remain unclear. This study integrated bulk and single-cell RNA-seq (scRNA-seq) from patients with stroke and mouse models to characterize circadian gene expression patterns. Using machine learning and consensus clustering, we identified a nine-gene circadian signature that distinguished patients with stroke and stratified them into three subtypes with distinct immune infiltration profiles. Single-cell RNA analyses highlighted microglia as key mediators, with DBP downregulation linked to microglial senescence. Experimental manipulation of DBP in microglial cells and a mouse stroke model demonstrated that DBP restoration reduced senescent phenotypes and infarct volume while improving neurological function. These findings establish circadian gene-based patient stratification and implicate microglial DBP as a modulator of post-stroke injury, offering potential avenues for risk assessment and targeted intervention.