美国南加州大学Giorgia Quadrato团队近期取得重要工作进展，他们研究开发了具有功能性浦肯野细胞的人类小脑类器官。相关研究成果2024年1月4日在线发表于《细胞—干细胞》杂志上。

据介绍，由于缺乏一个能够复现人类小脑细胞多样性和功能特征的基于人类细胞的系统，对人类小脑发育和疾病的研究一直受到阻碍。

研究人员报道了一种能够发展胎儿小脑复杂细胞多样性的人类类器官模型（人类小脑类器官[hCerO]），包括在本研究之前从未在体外产生过的人类特异性菱形唇祖细胞群体。2个月大的hCerO形成不同的细胞结构特征，包括层状组织分层，并在显示协调网络活动的抑制性和兴奋性神经元之间建立功能连接。hCerO的长期培养使浦肯野细胞能够健康存活和成熟，这些细胞显示出其体内对应细胞的分子和电生理特征，解决了该领域的长期挑战。

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。

附：英文原文

Title: Human cerebellar organoids with functional Purkinje cells

Author: Alexander Atamian, Marcella Birtele, Negar Hosseini, Tuan Nguyen, Anoothi Seth, Ashley Del Dosso, Sandeep Paul, Neil Tedeschi, Ryan Taylor, Marcelo P. Coba, Ranmal Samarasinghe, Carlos Lois, Giorgia Quadrato

Issue&Volume: 2024/01/04

Abstract: 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.

DOI: 10.1016/j.stem.2023.11.013

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00430-7