Exploratory Single-Cell Transcriptomic Profiling Reveals Dysregulated Glial Populations and Pathways in Focal...

Area of Science:

• Neuroscience
• Genomics
• Cell Biology

Background:

• Focal cortical dysplasia (FCD) is a leading cause of drug-resistant epilepsy.
• Understanding FCD pathogenesis at a cellular level is crucial but limited by bulk tissue studies.

Purpose of the Study:

• To investigate cell-type-specific molecular alterations in FCD using single-cell RNA sequencing.
• To identify shared molecular pathways disrupted across glial cell types in FCD.

Main Methods:

• Performed single-cell RNA sequencing (scRNA-seq) on FCD type II cortical tissue and matched control.
• Utilized Seurat for cell clustering, annotation, and differential gene expression analysis.
• Conducted Gene Ontology (GO) and KEGG pathway enrichment analyses.

Main Results:

• Observed a significant increase in microglia and astrocytes, and a decrease in oligodendrocytes in FCD cortex.
• Identified 128 differentially expressed genes (DEGs) common to glial populations, including upregulated RAC1 and downregulated ATP5F1D.
• Detected coordinated engagement of neuroinflammatory pathways (e.g., IL-17 signaling) and reduced intercellular communication.

Conclusions:

• FCD exhibits a convergent glial pathology with shared molecular disruptions in inflammation and metabolism.
• RAC1 and IL-17 signaling pathways are potential therapeutic targets for FCD-associated epileptogenesis.