A Multi-omics Atlas at Single-cell Resolution Revealing Key miRNA Regulatory Modules Driving Post-stroke Microglial Polarization

Abstract

: Ischemic stroke (IS) is the most common form of stroke. It triggers complex neuroinflammatory responses involving diverse cell populations within the central nervous system. Among these, microglia exhibit significant functional heterogeneity in IS. MicroRNAs (miRNAs), which regulate gene expression at the post-transcriptional level, are increasingly recognized as key modulators of neuroinflammation and potential biomarkers for IS; however, their specific relationships with microglial subtypes remain poorly defined. This research obtained 29 miRNAs through comparing correlation analysis between mRNA and miRNA. Through manual annotations and microglial populations, microglial functions are grouped into 5 groups. The process obtained increasing amounts of M1-like pro-inflammatory cells and decreasing amounts of M2-like anti-inflammatory populations. Several miRNAs, including miR-21-5p, let-7e-5p, miR-149-5p, miR-615-3p, and miR-218-5p, were shared across both M1 and M2, suggesting central roles in regulating polarization balance. Biological processes linked M1-associated targets to immunity, whereas M2-associated genes were enriched for cellular division and differentiation. These findings highlight miRNA-mediated networks that may shape microglial responses and influence IS progression. These findings provide insight into the mechanisms underlying microglial heterogeneity and offer potential directions for developing diagnostic biomarkers and therapeutic targets for ischemic stroke.