Single-cell RNA sequencing of adult primate neocortex reveals the regulatory dynamics of neural plasticity.

OBJECTIVES: To investigate gene expression dynamics in adult primate neocortex and elucidate the molecular basis of these capabilities. METHODS: Whole-cell transcriptome data from primary visual cortex (V1) of cynomolgus monkeys were analyzed, focusing on inhibitory neurons derived from the medial ganglionic eminence. Using RNA velocity and scVelo algorithms, we investigated subtle gene expression shifts, identified key driver genes, and conducted functional enrichment analysis. RESULTS: Our analysis revealed that somatostatin (SST)+ neurons are generated prior to parvalbumin (PVALB)+ neurons, with gene expression trajectories resembling those observed in developing animals. However, certain well-established SST+ and PVALB+ neurons, such as long-projecting SST+ chondrolectin (CHODL)+ neurons and PVALB+ unc-5 netrin receptor B (UNC5B)+ neurons, do not share the same lineage, suggesting distinct regulatory programs. Furthermore, we identified a set of genes strongly correlated with these trajectories, including dihydropyrimidinase like 3 (DPYSL3), osteocrin (OSTN), smoothelin (SMTN), meis homeobox 2 (MEIS2), chromodomain helicase DNA binding protein 3 (CHD3), and chromodomain helicase DNA binding protein 5 (CHD5). Functional enrichment analysis suggested that these genes are associated with neural plasticity and axon growth. CONCLUSIONS: This study provides novel insights into the gene expression dynamics of the primate neocortex. Genes involved in neuronal development and plasticity may underlie the advanced information-processing capabilities in primates.