Integrative genomic and spatial transcriptomic analysis elucidates the oligodendrocyte-mediated etiology of epileptic cortical thinning - PubMed
5 hours ago
- #oligodendrocytes
- #cortical thinning
- #focal epilepsy
- Integrative genomic and spatial transcriptomic analysis reveals that focal epilepsy and cortical thinning share a genetic basis.
- A latent factor (F-EpiCortex) links focal epilepsy to reduced cortical thickness, with cognitive function showing a protective association.
- Genetic analysis identifies oligodendrocytes as the key cellular mediator, with genes DPYSL5 and SLC16A8 providing robust protective effects.
- Spatial transcriptomic validation confirms oligodendrocyte enrichment in human cingulate and temporal cortices, aligning with cell-type-specific predictions.
- Experimental validation shows downregulation of protective proteins in human oligodendrocytes under excitotoxic stress, indicating susceptibility to epilepsy-associated injury.
- Findings suggest oligodendrocyte dysfunction as a shared genetic component, supporting a neurodevelopmental origin model alongside seizure-induced damage.