Ependymal cell lineage reprogramming as a potential therapeutic intervention for hydrocephalus.

IF 9 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL EMBO Molecular Medicine Pub Date : 2024-11-01 Epub Date: 2024-10-28 DOI:10.1038/s44321-024-00156-5
Konstantina Kaplani, Maria-Eleni Lalioti, Styliani Vassalou, Georgia Lokka, Evangelia Parlapani, Georgios Kritikos, Zoi Lygerou, Stavros Taraviras
{"title":"Ependymal cell lineage reprogramming as a potential therapeutic intervention for hydrocephalus.","authors":"Konstantina Kaplani, Maria-Eleni Lalioti, Styliani Vassalou, Georgia Lokka, Evangelia Parlapani, Georgios Kritikos, Zoi Lygerou, Stavros Taraviras","doi":"10.1038/s44321-024-00156-5","DOIUrl":null,"url":null,"abstract":"<p><p>Hydrocephalus is a common neurological condition, characterized by the excessive accumulation of cerebrospinal fluid in the cerebral ventricles. Primary treatments for hydrocephalus mainly involve neurosurgical cerebrospinal fluid diversion, which hold high morbidity and failure rates, highlighting the necessity for the discovery of novel therapeutic approaches. Although the pathophysiology of hydrocephalus is highly multifactorial, impaired function of the brain ependymal cells plays a fundamental role in hydrocephalus. Here we show that GemC1 and McIdas, key regulators of multiciliated ependymal cell fate determination, induce direct cellular reprogramming towards ependyma. Our study reveals that ectopic expression of GemC1 and McIdas reprograms cortical astrocytes and programs mouse embryonic stem cells into ependyma. McIdas is sufficient to establish functional activity in the reprogrammed astrocytes. Furthermore, we show that McIdas' expression promotes ependymal cell regeneration in two different postnatal hydrocephalus mouse models: an intracranial hemorrhage and a genetic form of hydrocephalus and ameliorates the cytoarchitecture of the neurogenic niche. Our study provides evidence on the restoration of ependyma in animal models mimicking hydrocephalus that could be exploited towards future therapeutic interventions.</p>","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.0000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"EMBO Molecular Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s44321-024-00156-5","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/28 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

Abstract

Hydrocephalus is a common neurological condition, characterized by the excessive accumulation of cerebrospinal fluid in the cerebral ventricles. Primary treatments for hydrocephalus mainly involve neurosurgical cerebrospinal fluid diversion, which hold high morbidity and failure rates, highlighting the necessity for the discovery of novel therapeutic approaches. Although the pathophysiology of hydrocephalus is highly multifactorial, impaired function of the brain ependymal cells plays a fundamental role in hydrocephalus. Here we show that GemC1 and McIdas, key regulators of multiciliated ependymal cell fate determination, induce direct cellular reprogramming towards ependyma. Our study reveals that ectopic expression of GemC1 and McIdas reprograms cortical astrocytes and programs mouse embryonic stem cells into ependyma. McIdas is sufficient to establish functional activity in the reprogrammed astrocytes. Furthermore, we show that McIdas' expression promotes ependymal cell regeneration in two different postnatal hydrocephalus mouse models: an intracranial hemorrhage and a genetic form of hydrocephalus and ameliorates the cytoarchitecture of the neurogenic niche. Our study provides evidence on the restoration of ependyma in animal models mimicking hydrocephalus that could be exploited towards future therapeutic interventions.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
脑外膜细胞系重编程作为治疗脑积水的一种潜在干预措施。
脑积水是一种常见的神经系统疾病,其特点是脑脊液在脑室过度积聚。脑积水的主要治疗方法是通过神经外科手术进行脑脊液引流,但这种方法的发病率和失败率都很高,因此有必要探索新的治疗方法。虽然脑积水的病理生理学具有高度的多因素性,但脑外膜细胞功能受损在脑积水中起着根本性的作用。在这里,我们发现 GemC1 和 McIdas(多纤毛外膜细胞命运决定的关键调控因子)可诱导细胞直接向外膜重编程。我们的研究发现,异位表达GemC1和McIdas可以重编程大脑皮层星形胶质细胞,并将小鼠胚胎干细胞编程为外膜。McIdas足以在重编程的星形胶质细胞中建立功能活性。此外,我们还发现,McIdas的表达可促进两种不同的出生后脑积水小鼠模型(颅内出血和遗传性脑积水)中的外膜细胞再生,并改善神经源龛的细胞结构。我们的研究提供了在模拟脑积水的动物模型中恢复外膜的证据,可用于未来的治疗干预。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
EMBO Molecular Medicine
EMBO Molecular Medicine 医学-医学:研究与实验
CiteScore
17.70
自引率
0.90%
发文量
105
审稿时长
4-8 weeks
期刊介绍: EMBO Molecular Medicine is an open access journal in the field of experimental medicine, dedicated to science at the interface between clinical research and basic life sciences. In addition to human data, we welcome original studies performed in cells and/or animals provided they demonstrate human disease relevance. To enhance and better specify our commitment to precision medicine, we have expanded the scope of EMM and call for contributions in the following fields: Environmental health and medicine, in particular studies in the field of environmental medicine in its functional and mechanistic aspects (exposome studies, toxicology, biomarkers, modeling, and intervention). Clinical studies and case reports - Human clinical studies providing decisive clues how to control a given disease (epidemiological, pathophysiological, therapeutic, and vaccine studies). Case reports supporting hypothesis-driven research on the disease. Biomedical technologies - Studies that present innovative materials, tools, devices, and technologies with direct translational potential and applicability (imaging technologies, drug delivery systems, tissue engineering, and AI)
期刊最新文献
Rett syndrome: interferon-γ to the rescue? A new class of capsid-targeting inhibitors that specifically block HIV-1 nuclear import. Jag1 insufficiency alters liver fibrosis via T cell and hepatocyte differentiation defects. Pre-clinical development of AP4B1 gene replacement therapy for hereditary spastic paraplegia type 47. Targeting USP11 regulation by a novel lithium-organic coordination compound improves neuropathologies and cognitive functions in Alzheimer transgenic mice.
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1