具有功能性浦肯野细胞的人类小脑器官组织

IF 19.8 1区 医学 Q1 CELL & TISSUE ENGINEERING Cell stem cell Pub Date : 2024-01-04 DOI:10.1016/j.stem.2023.11.013
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
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引用次数: 0

摘要

由于需要一种基于人类细胞的系统来再现人类小脑的细胞多样性和功能特征,有关人类小脑发育和疾病的研究一直受到阻碍。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]),它能够发育出胎儿小脑复杂的细胞多样性,包括人类特异的菱形唇祖细胞群,而在这项研究之前,这种祖细胞群从未在体外生成过。2个月大的hCerOs形成了明显的细胞结构特征,包括层状有组织分层,并在抑制性和兴奋性神经元之间建立了功能性连接,显示出协调的网络活动。长期培养 hCerOs 可使普肯列细胞健康存活和成熟,并显示出体内对应细胞的分子和电生理特征,从而解决了该领域长期存在的难题。因此,这项研究提供了一个与生理相关的全人类模型系统,用于阐明支配小脑发育和疾病的细胞类型特异性机制。
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Human cerebellar organoids with functional Purkinje cells

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.

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来源期刊
Cell stem cell
Cell stem cell 生物-细胞生物学
CiteScore
37.10
自引率
2.50%
发文量
151
审稿时长
42 days
期刊介绍: Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.
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