There is a pressing need to develop human cell-based models of the cerebellum, as mouse models lack human-specific features and do not fully recapitulate disease phenotypes. Using a cerebellar induction strategy based on in vivo developmental signaling molecules, Atamian et al. were able to generate 3D human organoids that reflected the major cell-type composition of the developing cerebellum, including Bergmann glia, granule cells and Purkinje cells. The organoids even included ventricular and subventricular rhombic lip progenitors — cell clusters only found in the human cerebellum. Long-term culture of these cerebellar organoids gave rise to functionally mature Purkinje cells that were capable of firing multiple action potentials, in an all-human culture system. Calcium imaging revealed coordinated spontaneous network activity across the organoids that was generated by both excitatory and inhibitory neurons. These models could provide valuable insights into human cerebellar development and into how this process can go awry in diseases such as Dandy–Walker syndrome and pediatric cancers.

迫切需要开发基于人类细胞的小脑模型，因为小鼠模型缺乏人类特异性特征并且不能完全重现疾病表型。Atamian 等人使用基于体内发育信号分子的小脑诱导策略。能够生成 3D 人体类器官，反映发育中小脑的主要细胞类型组成，包括伯格曼胶质细胞、颗粒细胞和浦肯野细胞。这些类器官甚至包括心室和心室下菱形唇祖细胞——仅在人类小脑中发现的细胞簇。这些小脑类器官的长期培养产生了功能成熟的浦肯野细胞，这些细胞能够在全人类培养系统中激发多种动作电位。钙成像揭示了由兴奋性和抑制性神经元产生的跨类器官协调的自发网络活动。这些模型可以为人类小脑发育以及这一过程如何在丹迪-沃克综合征和儿童癌症等疾病中出错提供宝贵的见解。