在人类多能干细胞模型中,诱导星形胶质细胞反应性会促进神经退行性变。

IF 5.9 2区 医学 Q1 CELL & TISSUE ENGINEERING
Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-08-01 DOI:10.1016/j.stemcr.2024.07.002
Cátia Gomes, Kang-Chieh Huang, Jade Harkin, Aaron Baker, Jason M Hughes, Yanling Pan, Kaylee Tutrow, Kirstin B VanderWall, Sailee S Lavekar, Melody Hernandez, Theodore R Cummins, Scott G Canfield, Jason S Meyer
{"title":"在人类多能干细胞模型中,诱导星形胶质细胞反应性会促进神经退行性变。","authors":"Cátia Gomes, Kang-Chieh Huang, Jade Harkin, Aaron Baker, Jason M Hughes, Yanling Pan, Kaylee Tutrow, Kirstin B VanderWall, Sailee S Lavekar, Melody Hernandez, Theodore R Cummins, Scott G Canfield, Jason S Meyer","doi":"10.1016/j.stemcr.2024.07.002","DOIUrl":null,"url":null,"abstract":"<p><p>Reactive astrocytes are known to exert detrimental effects upon neurons in several neurodegenerative diseases, yet our understanding of how astrocytes promote neurotoxicity remains incomplete, especially in human systems. In this study, we leveraged human pluripotent stem cell (hPSC) models to examine how reactivity alters astrocyte function and mediates neurodegeneration. hPSC-derived astrocytes were induced to a reactive phenotype, at which point they exhibited a hypertrophic profile and increased complement C3 expression. Functionally, reactive astrocytes displayed decreased intracellular calcium, elevated phagocytic capacity, and decreased contribution to the blood-brain barrier. Subsequently, co-culture of reactive astrocytes with a variety of neuronal cell types promoted morphological and functional alterations. Furthermore, when reactivity was induced in astrocytes from patient-specific hPSCs (glaucoma, Alzheimer's disease, and amyotrophic lateral sclerosis), the reactive state exacerbated astrocytic disease-associated phenotypes. These results demonstrate how reactive astrocytes modulate neurodegeneration, significantly contributing to our understanding of a role for reactive astrocytes in neurodegenerative diseases.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1122-1136"},"PeriodicalIF":5.9000,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368677/pdf/","citationCount":"0","resultStr":"{\"title\":\"Induction of astrocyte reactivity promotes neurodegeneration in human pluripotent stem cell models.\",\"authors\":\"Cátia Gomes, Kang-Chieh Huang, Jade Harkin, Aaron Baker, Jason M Hughes, Yanling Pan, Kaylee Tutrow, Kirstin B VanderWall, Sailee S Lavekar, Melody Hernandez, Theodore R Cummins, Scott G Canfield, Jason S Meyer\",\"doi\":\"10.1016/j.stemcr.2024.07.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Reactive astrocytes are known to exert detrimental effects upon neurons in several neurodegenerative diseases, yet our understanding of how astrocytes promote neurotoxicity remains incomplete, especially in human systems. In this study, we leveraged human pluripotent stem cell (hPSC) models to examine how reactivity alters astrocyte function and mediates neurodegeneration. hPSC-derived astrocytes were induced to a reactive phenotype, at which point they exhibited a hypertrophic profile and increased complement C3 expression. Functionally, reactive astrocytes displayed decreased intracellular calcium, elevated phagocytic capacity, and decreased contribution to the blood-brain barrier. Subsequently, co-culture of reactive astrocytes with a variety of neuronal cell types promoted morphological and functional alterations. Furthermore, when reactivity was induced in astrocytes from patient-specific hPSCs (glaucoma, Alzheimer's disease, and amyotrophic lateral sclerosis), the reactive state exacerbated astrocytic disease-associated phenotypes. These results demonstrate how reactive astrocytes modulate neurodegeneration, significantly contributing to our understanding of a role for reactive astrocytes in neurodegenerative diseases.</p>\",\"PeriodicalId\":21885,\"journal\":{\"name\":\"Stem Cell Reports\",\"volume\":\" \",\"pages\":\"1122-1136\"},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2024-08-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368677/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Stem Cell Reports\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.stemcr.2024.07.002\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/1 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stem Cell Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.stemcr.2024.07.002","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/1 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
引用次数: 0

摘要

已知反应性星形胶质细胞在几种神经退行性疾病中对神经元产生有害影响,但我们对星形胶质细胞如何促进神经毒性的了解仍不全面,尤其是在人类系统中。在这项研究中,我们利用人体多能干细胞(hPSC)模型来研究反应性如何改变星形胶质细胞的功能并介导神经退行性变。hPSC衍生的星形胶质细胞被诱导成反应性表型,此时它们表现出肥大特征并增加补体C3的表达。在功能上,反应性星形胶质细胞显示出细胞内钙减少、吞噬能力增强以及对血脑屏障的贡献减少。随后,将反应性星形胶质细胞与多种神经元细胞类型共培养会促进形态和功能的改变。此外,当从患者特异性 hPSCs(青光眼、阿尔茨海默病和肌萎缩侧索硬化症)中诱导星形胶质细胞的反应性时,反应性状态会加剧星形胶质细胞疾病相关表型。这些结果证明了反应性星形胶质细胞是如何调节神经退行性变的,极大地促进了我们对反应性星形胶质细胞在神经退行性疾病中的作用的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Induction of astrocyte reactivity promotes neurodegeneration in human pluripotent stem cell models.

Reactive astrocytes are known to exert detrimental effects upon neurons in several neurodegenerative diseases, yet our understanding of how astrocytes promote neurotoxicity remains incomplete, especially in human systems. In this study, we leveraged human pluripotent stem cell (hPSC) models to examine how reactivity alters astrocyte function and mediates neurodegeneration. hPSC-derived astrocytes were induced to a reactive phenotype, at which point they exhibited a hypertrophic profile and increased complement C3 expression. Functionally, reactive astrocytes displayed decreased intracellular calcium, elevated phagocytic capacity, and decreased contribution to the blood-brain barrier. Subsequently, co-culture of reactive astrocytes with a variety of neuronal cell types promoted morphological and functional alterations. Furthermore, when reactivity was induced in astrocytes from patient-specific hPSCs (glaucoma, Alzheimer's disease, and amyotrophic lateral sclerosis), the reactive state exacerbated astrocytic disease-associated phenotypes. These results demonstrate how reactive astrocytes modulate neurodegeneration, significantly contributing to our understanding of a role for reactive astrocytes in neurodegenerative diseases.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Stem Cell Reports
Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY
CiteScore
10.50
自引率
1.70%
发文量
200
审稿时长
28 weeks
期刊介绍: Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信