Organoid techniques provide unique platforms to model brain development and neurological disorders. Whereas several methods for recapitulating corticogenesis have been described, a system modeling human medial ganglionic eminence (MGE) development, a critical ventral brain domain producing cortical interneurons and related lineages, has been lacking until recently. Here, we describe the generation of MGE and cortex-specific organoids from human pluripotent stem cells that recapitulate the development of MGE and cortex domains, respectively. Population and single-cell RNA sequencing (RNA-seq) profiling combined with bulk assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) analyses revealed transcriptional and chromatin accessibility dynamics and lineage relationships during MGE and cortical organoid development. Furthermore, MGE and cortical organoids generated physiologically functional neurons and neuronal networks. Finally, fusing region-specific organoids followed by live imaging enabled analysis of human interneuron migration and integration. Together, our study provides a platform for generating domain-specific brain organoids and modeling human interneuron migration and offers deeper insight into molecular dynamics during human brain development.

中文翻译：

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融合了特定于地区的hPSC衍生的类器官模型，可模拟人脑发育和中间神经元迁移。

类器官技术为建模大脑发育和神经系统疾病提供了独特的平台。尽管已经描述了几种概括皮层发生的方法，但是直到最近，仍缺乏一个模拟人内侧神经节突（MGE）发育，产生皮层中间神经元和相关谱系的关键腹侧脑域的系统。在这里，我们描述了人类多能干细胞分别概述MGE和皮质域发展的MGE和皮质特定类器官的生成。群体和单细胞RNA测序（RNA-seq）谱图与大量测定相结合的转座可及染色质的高通量测序（ATAC-seq）分析揭示了MGE和皮质类器官发育过程中的转录和染色质可及动力学和谱系关系。此外，MGE和皮层类器官产生生理功能的神经元和神经元网络。最后，融合区域特定的类器官，然后进行实时成像，可以分析人间神经元的迁移和整合。在一起，我们的研究提供了一个平台，用于生成特定领域的大脑类器官，并为人类中间神经元迁移建模，并为人类大脑发育过程中的分子动力学提供了更深入的见解。