Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Spatial Genomics, 145 Vista Avenue Suite 111, Pasadena, CA 91107, USA.
Cell Stem Cell. 2024 Jan 4;31(1):39-51.e6. doi: 10.1016/j.stem.2023.11.013.
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 in vitro 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 in vivo 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.
人类小脑发育和疾病的研究一直受到需要一种基于人类细胞的系统的阻碍，该系统能够重现人类小脑的细胞多样性和功能特征。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]），它能够发育出复杂的细胞多样性，包括人类特有的菱形唇祖细胞群体，在此之前，这些细胞从未在体外产生过。2 个月大的 hCerOs 形成了独特的细胞结构特征，包括层状组织层，并且在抑制性和兴奋性神经元之间建立了功能连接，这些神经元显示出协调的网络活动。hCerOs 的长期培养允许浦肯野细胞的健康存活和成熟，这些细胞表现出与其体内对应物的分子和电生理特征，解决了该领域的一个长期挑战。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。
