Abstract：
The cerebellum has historically been primarily associated with the regulation of precise motor functions. However, recent findings suggest that it also plays a pivotal role in the development of advanced cognitive functions, including learning, memory, and emotion regulation. Pathological changes in the cerebellum, whether congenital hereditary or acquired degenerative, can result in a diverse spectrum of disorders, ranging from genetic spinocerebellar ataxias to psychiatric conditions such as autism, and schizophrenia. While studies in animal models have significantly contributed to our understanding of the genetic networks governing cerebellar development, it is important to note that the human cerebellum follows a protracted developmental timeline compared to the neocortex. Consequently, employing animal models to uncover human-specific molecular events in cerebellar development presents significant challenges. The emergence of human induced pluripotent stem cells (hiPSCs) has provided an invaluable tool for creating human-based culture systems, enabling the modeling and analysis of cerebellar physiology and pathology. hiPSCs and their differentiated progenies can be derived from patients with specific disorders or carrying distinct genetic variants. Importantly, they preserve the unique genetic signatures of the individuals from whom they originate, allowing for the elucidation of human-specific molecular and cellular processes involved in cerebellar development and related disorders. This review focuses on the technical advancements in the utilization of hiPSCs for the generation of both 2D cerebellar neuronal cells and 3D cerebellar organoids.
摘要：
小脑历来主要与精确运动功能的调节有关。然而,最近的发现表明，它在高级认知功能的发展中也起着关键作用，包括学习,记忆,和情绪调节。小脑的病理变化,无论是先天性遗传性还是获得性退行性，会导致各种各样的疾病，从遗传性脊髓小脑共济失调到自闭症等精神疾病，和精神分裂症。虽然动物模型的研究极大地促进了我们对控制小脑发育的遗传网络的理解，值得注意的是，与大脑皮层相比，人类小脑遵循的是一个漫长的发育时间线。因此,采用动物模型来揭示小脑发育中人类特异性分子事件是一项重大挑战.人类诱导多能干细胞（hiPSCs）的出现为创建基于人类的培养系统提供了宝贵的工具，能够对小脑生理和病理进行建模和分析。hiPSC及其分化后代可以来源于患有特定疾病或携带不同遗传变体的患者。重要的是,它们保留了它们起源的个体的独特遗传特征，允许阐明涉及小脑发育和相关疾病的人类特异性分子和细胞过程。这篇综述的重点是利用hiPSCs产生2D小脑神经元细胞和3D小脑类器官的技术进步。
