Identification and validation of microglia-associated genes in ischemic stroke using single-cell and bulk RNA-seq

Area of Science:

• Neuroscience
• Genomics
• Immunology

Background:

• Ischemic stroke (IS) is a leading cause of death with unclear microglial mechanisms.
• Understanding microglia's role is crucial for developing effective IS treatments.

Purpose of the Study:

• To identify key genes related to microglia in IS pathogenesis.
• To elucidate the molecular mechanisms underlying these genes' roles in IS.

Main Methods:

• Transcriptome data analysis of IS patients.
• Identification of differentially expressed genes (DEGs) and microglia-related genes (MGGs).
• Protein-protein interaction (PPI) analysis, enrichment analysis, regulatory network construction, drug prediction, and qRT-PCR validation in mouse models.

Main Results:

• 3 key genes (Cd14, Csf1, Tlr2) were identified from 1407 DEGs and 100 MGGs.
• These genes are co-enriched in pathways like leishmania infection and ribosomal.
• Cd14, Csf1, and Tlr2 showed significantly elevated expression in a mouse model of IS (tMCAO) and are regulated by miRNAs and TFs.
• Tlr2 and Adapalene showed strong molecular binding affinity.

Conclusions:

• Cd14, Csf1, and Tlr2 are validated as key genes in IS pathogenesis.
• These genes represent potential novel diagnostic and therapeutic targets for ischemic stroke.