GABAergic interneurons (GINs) are a heterogeneous population of inhibitory neurons that collectively contribute to the maintenance of normal neuronal excitability and network activity. Identification of the genetic regulatory elements and transcription factors that contribute toward GIN function may provide new insight into the pathways underlying proper GIN activity while also indicating potential therapeutic targets for GIN-associated disorders, such as schizophrenia and epilepsy. In this study, we examined the temporal changes in gene expression and chromatin accessibility during GIN development by performing transcriptomic and epigenomic analyses on human induced pluripotent stem cell-derived neurons at 22, 50 and 78 days (D) post-differentiation. We observed 13 221 differentially accessible regions (DARs) of chromatin that associate with temporal changes in gene expression at D78 and D50, relative to D22. We also classified families of transcription factors that are increasingly enriched at DARs during differentiation, indicating regulatory networks that likely drive GIN development. Collectively, these data provide a resource for examining the molecular networks regulating GIN functionality.

中文翻译：

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与人类 iPSC 衍生的 GABA 能中间神经元发育相关的转录组和表观基因组动力学。

GABA 能中间神经元 (GIN) 是抑制性神经元的异质群体，共同有助于维持正常的神经元兴奋性和网络活动。鉴定有助于 GIN 功能的遗传调控元件和转录因子可能为了解 GIN 适当活性的途径提供新的见解，同时也表明 GIN 相关疾病（例如精神分裂症和癫痫）的潜在治疗靶点。在这项研究中，我们通过对分化后 22、50 和 78 天 (D) 的人诱导多能干细胞衍生神经元进行转录组和表观基因组分析，检查了 GIN 发育过程中基因表达和染色质可及性的时间变化。我们观察到 13 221 个染色质差异可及区域 (DAR)，这些区域与 D78 和 D50 相对于 D22 基因表达的时间变化相关。我们还对分化过程中 DAR 处日益富集的转录因子家族进行了分类，表明可能推动 GIN 发展的调控网络。总的来说，这些数据为检查调节 GIN 功能的分子网络提供了资源。