Integrated Transcriptomic and Single-Cell Sequencing Identifies Altered Expression of Circadian Rhythm-Related Genes Pomc and Bmp4 in Post-Stroke Depression.

Abstract

Post-stroke depression (PSD) is a serious complication that significantly hinders stroke patients' recovery and quality of life. Uncovering the molecular changes that drive PSD is vital for understanding how depression develops following a stroke. In this study, we established a reproducible PSD model using minimally invasive photochemical-induced focal cortical lesion. Transcriptomic sequencing demonstrated that dysregulation of circadian entrainment genes is a central pathway in the development of post-stroke depressive-like behaviors. Protein-protein interaction network analysis of these circadian rhythm-related genes identified six hub genes. Four of these, including Pomc and Bmp4, exhibited expression patterns consistent with experimental validation. Integrated single-cell transcriptomic analysis further pinpointed cell-type-specific expression abnormalities of Pomc in endothelial cells and Bmp4 in oligodendrocytes. Subsequently, in silico perturbation analysis further indicated that their shared underlying regulatory mechanisms involve cell adhesion and extracellular matrix interaction. Collectively, using transcriptomic and single-cell sequencing in a PSD model, this study revealed altered expression patterns of circadian rhythm-related genes, providing potential targets for further investigation into the pathogenesis of PSD.