Spatial transcriptomics in epilepsy research: Early successes, opportunities, and challenges

Epilepsy affects more than 70 million people worldwide 1 and remains an important cause of global disability and mortality.2 Despite treatment advances, >30% of all epilepsies remain refractory to medication.[3][4][5] Improving the mechanistic understanding of epilepsy pathogenesis remains a critical unmet need.6 Epilepsy is often conceptualized as a disease of brain networks, not only as derangements within a connectome of neurons and network hubs, 7 but also as pathological changes within an interactome of molecular processes among neurons and surrounding glia.8 Considering this conceptual framework, 9 understanding the spatial relationship and interaction among cells within epilepsy networks is crucial.Transcriptomics, as a method of characterizing cellular gene expression through sequencing mRNA, has rapidly advanced understanding of human brain cellular diversity.Transcriptomic sequencing technology has quickly evolved through three stages: bulk sequencing, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics (ST; Figure 1). 11The evolution from bulk to singlecell sequencing 12 has revealed thousands of regionally specific brain cell types, 13 with individual cortical areas