Mouse and human share conserved transcriptional programs for interneuron development

Genetic variation confers susceptibility to neurodevelopmental disorders by affecting the development of specific cell types. Changes in cortical and striatal ?-aminobutyric acid-expressing (GABAergic) neurons are common in autism and schizophrenia. Here we used single-cell RNA sequencing to characterize the emergence of cell diversity in the human ganglionic eminences, the transitory structures of the human fetal brain where striatal and cortical GABAergic neurons are generated. We identified regional and temporal diversity among progenitor cells underlying the generation of a variety of projection neurons and interneurons. We found that these cells are specified within the human ganglionic eminences by gene regulatory networks similar to those previously identified in rodents. Our findings reveal an evolutionarly conserved regulatory logic controlling the specification, migration, and differentiation of GABAergic neurons in the human telencephalon. Overall design: The human ganglionic eminences at GW09, GW11, GW12, GW13, GW16 and GW18 were dissociated for single-cell RNA-seq (10x Genomics Chromium)

遗传变异通过影响特定细胞类型的发育，赋予个体神经发育障碍易感性。自闭症与精神分裂症患者中，皮层与纹状体γ-氨基丁酸能（GABAergic）神经元的异常改变较为普遍。本研究借助单细胞RNA测序（single-cell RNA-seq）技术，对人类神经节隆起（ganglionic eminences）的细胞多样性起源过程进行表征；神经节隆起是人类胎儿脑中生成纹状体与皮层GABA能神经元的暂时性结构。本研究鉴定出多种投射神经元与中间神经元生成过程中，祖细胞所具备的区域与时间维度多样性。研究发现，人类神经节隆起内的此类细胞，其特化过程所依赖的基因调控网络与此前在啮齿类动物中鉴定到的调控网络高度相似。本研究结果揭示了一套进化保守的调控逻辑，该逻辑管控着人类端脑内GABA能神经元的特化、迁移与分化过程。实验整体设计：采集孕龄GW09、GW11、GW12、GW13、GW16及GW18周的人类神经节隆起组织，经解离处理后采用10x Genomics Chromium平台开展单细胞RNA测序。