Research on human cerebellar development and disease has been hampered by the need for a human cell-based system that recapitulates the human cerebellum’s cellular diversity and functional features. Here, we report a human organoid model (human cerebellar organoids [hCerOs]) capable of developing the complex cellular diversity of the fetal cerebellum, including a human-specific rhombic lip progenitor population that have never been generated prior to this study. 2-month-old hCerOs form distinct cytoarchitectural features, including laminar organized layering, and create functional connections between inhibitory and excitatory neurons that display coordinated network activity. Long-term culture of hCerOs allows healthy survival and maturation of Purkinje cells that display molecular and electrophysiological hallmarks of their counterparts, addressing a long-standing challenge in the field. This study therefore provides a physiologically relevant, all-human model system to elucidate the cell-type-specific mechanisms governing cerebellar development and disease.

中文翻译：

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具有功能性浦肯野细胞的人小脑类器官

对人类小脑发育和疾病的研究因需要一种基于人类细胞的系统来概括人类小脑的细胞多样性和功能特征而受到阻碍。在这里，我们报告了一种人类类器官模型（人类小脑类器官 [hCerOs]），该模型能够发育胎儿小脑的复杂细胞多样性，包括在本研究之前从未生成的人类特异性菱形唇祖细胞群。2 个月大的 hCerO 形成独特的细胞结构特征，包括层状组织分层，并在抑制性和兴奋性神经元之间建立功能连接，显示协调的网络活动。hCerO 的长期培养可以使浦肯野细胞健康存活和成熟，这些细胞显示出其对应细胞的分子和电生理学特征，解决了该领域长期存在的挑战。因此，这项研究提供了一个生理相关的全人类模型系统，以阐明控制小脑发育和疾病的细胞类型特异性机制。