Spatial transcriptomics reveals laminar and cell-type-specific A-to-I RNA editing signatures in the macaque cortex

Abstract

ADAR-mediated A-to-I RNA editing is crucial for proper neuronal function. However, its spatial signatures in the cerebral cortex remain largely unexplored. To address this, we developed SRDRE, an analysis framework for identifying RNA editing sites in spatial transcriptomics data. By analyzing over 40 million cells across 142 spatially annotated cortical regions in the adult macaque cortex, we uncovered laminar and cell-type-specific RNA editing landscapes. Notably, neuronal RNA editing levels correlated with cortical hierarchy in the visual and somatosensory systems. Parvalbumin neurons exhibited the highest editing activity in most regions. Furthermore, we identified primate-enriched sites within ion channel genes, specifically in excitatory neuronal subtypes of the prefrontal cortex. Finally, in a preliminary exploratory analysis, we observed altered RNA editing in deeper layers of the dorsolateral prefrontal cortex in macaques exhibiting depressive-like behaviors, suggesting a potential link that warrants further investigation. These findings underscore the role of RNA editing and its potential contributions to cortical specialization, brain evolution, and neuropsychiatric disorders. ADAR-mediated RNA editing is crucial for neuronal function, yet its spatial signatures in the cortex are unknown. Here, authors show that editing correlates with cortical hierarchy, and PV neurons exhibit the highest editing levels in most regions.