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
{"title":"具有功能性浦肯野细胞的人类小脑器官组织","authors":"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","doi":"10.1016/j.stem.2023.11.013","DOIUrl":null,"url":null,"abstract":"<p>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 <em>in vitro</em><span> 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 </span><em>in vivo</em> 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.</p>","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":null,"pages":null},"PeriodicalIF":19.8000,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Human cerebellar organoids with functional Purkinje cells\",\"authors\":\"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\",\"doi\":\"10.1016/j.stem.2023.11.013\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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 <em>in vitro</em><span> 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 </span><em>in vivo</em> 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.</p>\",\"PeriodicalId\":9665,\"journal\":{\"name\":\"Cell stem cell\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":19.8000,\"publicationDate\":\"2024-01-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell stem cell\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.stem.2023.11.013\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell stem cell","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.stem.2023.11.013","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
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.
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.