Activity-dependent regulome and transcriptome of human GABAergic neurons reveal new patterns of gene regulation and neurological disease heritability

Neuronal activity-dependent gene expression is essential for healthy brain development. Emerging studies implicate alterations in GABAergic neuronal circuits in neurodevelopmental and psychiatric disorders. We conducted an activity-dependent transcriptional and epigenetic profiling of human iPSC-derived GABAergic neurons. iCell GABAneurons were characterized by total and single-cell RNA sequencing and found to have similar transcriptional profiles to developing subcortical GABAergic neurons. These cultures were grown for 14-16 days in vitro prior to silencing with 2-amino-5-phosphonopentanoic acid and tetrodotoxin for 12 hours, followed by stimulation with 55mM potassium chloride for various time points prior to harvesting cells for RNA sequencing, ATAC sequencing or ChIP sequencing.