• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

脑类器官中重现 POLG 疾病的标志性分子和病理学特征。

Hallmark Molecular and Pathological Features of POLG Disease are Recapitulated in Cerebral Organoids.

机构信息

Department of Clinical Medicine (K1), University of Bergen, Bergen, 5021, Norway.

Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 20092, China.

出版信息

Adv Sci (Weinh). 2024 May;11(18):e2307136. doi: 10.1002/advs.202307136. Epub 2024 Mar 6.

DOI:10.1002/advs.202307136
PMID:38445970
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11095234/
Abstract

In this research, a 3D brain organoid model is developed to study POLG-related encephalopathy, a mitochondrial disease stemming from POLG mutations. Induced pluripotent stem cells (iPSCs) derived from patients with these mutations is utilized to generate cortical organoids, which exhibited typical features of the diseases with POLG mutations, such as altered morphology, neuronal loss, and mitochondiral DNA (mtDNA) depletion. Significant dysregulation is also identified in pathways crucial for neuronal development and function, alongside upregulated NOTCH and JAK-STAT signaling pathways. Metformin treatment ameliorated many of these abnormalities, except for the persistent affliction of inhibitory dopamine-glutamate (DA GLU) neurons. This novel model effectively mirrors both the molecular and pathological attributes of diseases with POLG mutations, providing a valuable tool for mechanistic understanding and therapeutic screening for POLG-related disorders and other conditions characterized by compromised neuronal mtDNA maintenance and complex I deficiency.

摘要

在这项研究中，开发了一种 3D 脑类器官模型，用于研究 POLG 相关脑病，这是一种源自 POLG 突变的线粒体疾病。利用源自这些突变患者的诱导多能干细胞（iPSC）生成皮质类器官，这些类器官表现出具有 POLG 突变的疾病的典型特征，例如形态改变、神经元丧失和线粒体 DNA（mtDNA）耗竭。在神经元发育和功能至关重要的途径中也发现了显著的失调，同时上调了 NOTCH 和 JAK-STAT 信号通路。二甲双胍治疗改善了许多这些异常，除了持续存在的抑制性多巴胺-谷氨酸（DA GLU）神经元的困扰。这种新型模型有效地反映了具有 POLG 突变的疾病的分子和病理特征，为 POLG 相关疾病和其他以神经元 mtDNA 维持和复合物 I 缺陷为特征的疾病的机制理解和治疗筛选提供了有价值的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/b6e2d3a9bd52/ADVS-11-2307136-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/e621a722e000/ADVS-11-2307136-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/cf8b03dd003c/ADVS-11-2307136-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/bd63618fb6eb/ADVS-11-2307136-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/31d200a848b9/ADVS-11-2307136-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/cc9bdb3a1c09/ADVS-11-2307136-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/77a38d1471fa/ADVS-11-2307136-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/f1faf4344736/ADVS-11-2307136-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/3787da91ed21/ADVS-11-2307136-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/b6e2d3a9bd52/ADVS-11-2307136-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/e621a722e000/ADVS-11-2307136-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/cf8b03dd003c/ADVS-11-2307136-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/bd63618fb6eb/ADVS-11-2307136-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/31d200a848b9/ADVS-11-2307136-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/cc9bdb3a1c09/ADVS-11-2307136-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/77a38d1471fa/ADVS-11-2307136-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/f1faf4344736/ADVS-11-2307136-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/3787da91ed21/ADVS-11-2307136-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf11/11095234/b6e2d3a9bd52/ADVS-11-2307136-g007.jpg

相似文献

1
Hallmark Molecular and Pathological Features of POLG Disease are Recapitulated in Cerebral Organoids.脑类器官中重现 POLG 疾病的标志性分子和病理学特征。
Adv Sci (Weinh). 2024 May;11(18):e2307136. doi: 10.1002/advs.202307136. Epub 2024 Mar 6.
2
Activation of Neurotoxic Astrocytes Due to Mitochondrial Dysfunction Triggered by Mutation.由于突变导致线粒体功能障碍而引发的神经毒性星形胶质细胞的激活。
Int J Biol Sci. 2024 May 11;20(8):2860-2880. doi: 10.7150/ijbs.93445. eCollection 2024.
3
Deoxyribonucleoside treatment rescues EtBr-induced mtDNA depletion in iPSC-derived neural stem cells with POLG mutations.脱氧核苷处理挽救了具有 POLG 突变的 iPSC 衍生神经干细胞中 EtBr 诱导的 mtDNA 耗竭。
FASEB J. 2023 Sep;37(9):e23139. doi: 10.1096/fj.202300650RR.
4
The NAD Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC derived Cortical Organoid of Alpers' Disease.烟酰胺核糖核苷酸作为 NAD 前体可挽救 Alpers 病诱导多能干细胞来源皮质类器官中的线粒体缺陷和神经元丢失。
Int J Biol Sci. 2024 Jan 25;20(4):1194-1217. doi: 10.7150/ijbs.91624. eCollection 2024.
5
N-acetylcysteine amide ameliorates mitochondrial dysfunction and reduces oxidative stress in hiPSC-derived dopaminergic neurons with POLG mutation.N-乙酰半胱氨酸酰胺可改善 POLG 突变诱导的人诱导多能干细胞源性多巴胺能神经元线粒体功能障碍和氧化应激。
Exp Neurol. 2021 Mar;337:113536. doi: 10.1016/j.expneurol.2020.113536. Epub 2020 Nov 29.
6
POLG genotype influences degree of mitochondrial dysfunction in iPSC derived neural progenitors, but not the parent iPSC or derived glia.POLG 基因型影响 iPSC 衍生神经祖细胞中线粒体功能障碍的程度，但不影响亲本 iPSC 或衍生的神经胶质细胞。
Exp Neurol. 2023 Jul;365:114429. doi: 10.1016/j.expneurol.2023.114429. Epub 2023 Apr 25.
7
iPSC-Derived Neurons from Patients with POLG Mutations Exhibit Decreased Mitochondrial Content and Dendrite Simplification.来自携带 POLG 突变的患者的 iPSC 衍生神经元表现出线粒体含量减少和树突简化。
Am J Pathol. 2023 Feb;193(2):201-212. doi: 10.1016/j.ajpath.2022.11.002. Epub 2022 Nov 19.
8
Disease-specific phenotypes in iPSC-derived neural stem cells with POLG mutations.具有 POLG 突变的 iPSC 衍生神经干细胞中的疾病特异性表型。
EMBO Mol Med. 2020 Oct 7;12(10):e12146. doi: 10.15252/emmm.202012146. Epub 2020 Aug 25.
9
Voluntary wheel running has no impact on brain and liver mitochondrial DNA copy number or mutation measures in the PolG mouse model of aging.自愿轮跑对衰老的 PolG 小鼠模型的大脑和肝脏线粒体 DNA 拷贝数或突变测量没有影响。
PLoS One. 2020 Mar 2;15(3):e0226860. doi: 10.1371/journal.pone.0226860. eCollection 2020.
10
POLG-related disorders and their neurological manifestations.POLG 相关疾病及其神经表现。
Nat Rev Neurol. 2019 Jan;15(1):40-52. doi: 10.1038/s41582-018-0101-0.

引用本文的文献

1
Cannabinerol Restores mRNA Splicing Defects Induced by β-Amyloid in an In Vitro Model of Alzheimer's Disease: A Transcriptomic Study.大麻二酚在阿尔茨海默病体外模型中恢复由β-淀粉样蛋白诱导的mRNA剪接缺陷：一项转录组学研究
Int J Mol Sci. 2025 Mar 28;26(7):3113. doi: 10.3390/ijms26073113.
2
Biomedical applications of organoids in genetic diseases.类器官在遗传疾病中的生物医学应用。
Med Rev (2021). 2024 Dec 24;5(2):152-163. doi: 10.1515/mr-2024-0077. eCollection 2025 Apr.

本文引用的文献

1
Astrocytic pathology in Alpers' syndrome.星型胶质细胞病理学在 Alpers 综合征中的表现。
Acta Neuropathol Commun. 2023 May 31;11(1):86. doi: 10.1186/s40478-023-01579-w.
2
Modulating Mitochondrial DNA Heteroplasmy with Mitochondrially Targeted Endonucleases.用靶向线粒体的核酸内切酶调节线粒体 DNA 异质性
Ann Biomed Eng. 2024 Sep;52(9):2627-2640. doi: 10.1007/s10439-022-03051-7. Epub 2022 Aug 24.
3
Mitochondrial Respiratory Chain Dysfunction-A Hallmark Pathology of Idiopathic Parkinson's Disease?线粒体呼吸链功能障碍——特发性帕金森病的标志性病理特征？
Front Cell Dev Biol. 2022 Apr 1;10:874596. doi: 10.3389/fcell.2022.874596. eCollection 2022.
4
mutations lead to abnormal mitochondrial remodeling during neural differentiation of human pluripotent stem cells via SIRT3/AMPK pathway inhibition.突变通过 SIRT3/AMPK 通路抑制导致人多能干细胞神经分化过程中线粒体异常重塑。
Cell Cycle. 2022 Jun;21(11):1178-1193. doi: 10.1080/15384101.2022.2044136. Epub 2022 Mar 17.
5
as a Tool for Studying Mutations in Nuclear Genes Involved in Diseases Caused by Mitochondrial DNA Instability.作为研究与线粒体 DNA 不稳定性引起的疾病相关的核基因突变的工具。
Genes (Basel). 2021 Nov 24;12(12):1866. doi: 10.3390/genes12121866.
6
Flow Cytometric Analysis of Multiple Mitochondrial Parameters in Human Induced Pluripotent Stem Cells and Their Neural and Glial Derivatives.流式细胞术分析人诱导多能干细胞及其神经和神经胶质衍生物中的多个线粒体参数。
J Vis Exp. 2021 Nov 8(177). doi: 10.3791/63116.
7
Disruption of mitochondrial complex I induces progressive parkinsonism.线粒体复合物 I 的破坏会导致进行性帕金森病。
Nature. 2021 Nov;599(7886):650-656. doi: 10.1038/s41586-021-04059-0. Epub 2021 Nov 3.
8
Human ALS/FTD brain organoid slice cultures display distinct early astrocyte and targetable neuronal pathology.人肌萎缩侧索硬化症/额颞叶痴呆脑类器官切片培养物显示出明显的早期星形胶质细胞和可靶向神经元病理学。
Nat Neurosci. 2021 Nov;24(11):1542-1554. doi: 10.1038/s41593-021-00923-4. Epub 2021 Oct 21.
9
scMRMA: single cell multiresolution marker-based annotation.scMRMA：基于多重分辨率标记的单细胞注释。
Nucleic Acids Res. 2022 Jan 25;50(2):e7. doi: 10.1093/nar/gkab931.
10
Nicotinamide Riboside and Metformin Ameliorate Mitophagy Defect in Induced Pluripotent Stem Cell-Derived Astrocytes With Mutations.烟酰胺核糖苷和二甲双胍改善诱导多能干细胞来源的突变星形胶质细胞中的线粒体自噬缺陷。
Front Cell Dev Biol. 2021 Sep 24;9:737304. doi: 10.3389/fcell.2021.737304. eCollection 2021.