hiPSC 分化为小脑神经元细胞的进展。
Advances in the Differentiation of hiPSCs into Cerebellar Neuronal Cells.
发表日期:2024 Jul 18
作者:
Yingxin Wang, Wenzhu Liu, Yichang Jiao, Yitong Yang, Didi Shan, Xinbo Ji, Rui Zhang, Zexin Zhan, Yao Tang, Dandan Guo, Chuanzhu Yan, Fuchen Liu
来源:
Stem Cell Reviews and Reports
摘要:
小脑历来主要与精确运动功能的调节有关。然而,最近的研究结果表明,它在高级认知功能的发展中也发挥着关键作用,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后天性退行性病变,都可能导致多种疾病,从遗传性脊髓小脑性共济失调到自闭症和精神分裂症等精神疾病。虽然动物模型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,但值得注意的是,与新皮质相比,人类小脑的发育时间表较长。因此,利用动物模型来揭示小脑发育中人类特有的分子事件提出了重大挑战。人类诱导多能干细胞(hiPSC)的出现为创建基于人类的培养系统提供了宝贵的工具,从而能够对小脑生理学和病理学进行建模和分析。 hiPSC 及其分化后代可以源自患有特定疾病或携带不同遗传变异的患者。重要的是,它们保留了其起源个体的独特遗传特征,从而可以阐明参与小脑发育和相关疾病的人类特异性分子和细胞过程。本综述重点关注利用 hiPSC 生成 2D 小脑神经元细胞和 3D 小脑类器官的技术进步。© 2024。作者获得 Springer Science Business Media, LLC(Springer Nature 旗下子公司)的独家许可。
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.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.