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

ABSTRACT: Neuronal activity-dependent gene expression is essential for brain development. Although transcriptional and epigenetic effects of neuronal activity have been explored in mice, such an investigation is lacking in humans. Because alterations in GABAergic neuronal circuits are implicated in neurological disorders, we conducted a comprehensive activity-dependent transcriptional and epigenetic profiling of human induced pluripotent stem cell-derived GABAergic neurons similar to those of the early developing striatum. We identified genes whose expression is inducible after membrane depolarization, some of which have specifically evolved in primates and/or are associated with neurological diseases, including schizophrenia and autism spectrum disorder (ASD). We define the genome-wide profile of h

SUBMITTER: Boulting GL 

PROVIDER: S-EPMC7933108 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature