Single Cell Transcriptomics of Refractory Epilepsy patients in Colombia

Abstract

Maintaining electrical signaling homeostasis in the human neocortex relies on cell-type specific gene expression programs. However, when these programs are disrupted, the resulting imbalances can contribute to the pathogenesis of neurological disorders like epilepsy. Genetic factors are particularly implicated in a specific subtype of epilepsy known as refractory epilepsy or drug-resistant epilepsy (RE/DRE). This study shows the main results of the analysis of single cell transcriptomics for five pediatric RE patients in Colombia. A total of six samples obtained through surgical resection were analyzed by single-nuclei RNA sequencing (snRNA-seq). The genome of one patient was sequenced using high fidelity long-read sequencing. Functional enrichment of differentially expressed genes (DEGs) revealed glia-driven dysregulation of synaptic signaling, impaired glial-neuronal communication, and altered expression of genes related to neurotransmitter transport and calcium signaling. Activation of taste receptors in neurons was associated with neuroinflammatory processes. Structural variants were detected in genes associated with alterations of expression in specific cell types. This new data resource increases the diversity of information needed to develop new strategies for diagnosis of refractory epilepsy.