Bulk and single-cell RNA-seq analyses characterize a DBP-related circadian signature in ischemic stroke.

Authors

Wen Song, Yafang Liu, Le Zeng, Dong Cao, Jiachong Han, Jinbei Wen, Zeqi Huang, Liping Miao, Zhaoxia Liao, Chuwen Hu

Published in

iScience. Volume 29. Issue 8. Pages 117036. Aug 21, 2026. Epub Jul 31, 2026.

Abstract

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.

PMID:
42572586
Bibliographic data and abstract were imported from PubMed on 10 Aug 2026.

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