暴露在病理条件下可能需要细胞分泌含有mtDNA畸变的外泌体

IF 1.3 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Manjusha Vaidya, Sandeep Sreerama, Mariana Gaviria, K. Sugaya
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引用次数: 2

摘要

外泌体是所有细胞分泌的纳米囊泡,通过传递包含DNA、RNA和蛋白质的生物活性货物来进行细胞间通信。这些生物分子反映了其母体细胞的状态,并可能因病理条件而改变。因此,研究人员一直在研究与外泌体相关的DNA的差异序列和数量,作为疾病的有价值的生物标志物。外泌体携带不同类型的DNA分子,包括基因组、细胞质和线粒体(mtDNA)。据报道,mtDNA异常是涉及氧化应激的疾病的标志,如癌症和神经退行性疾病。建立包括适当细胞谱系的强大体外模型是研究疾病特异性异常和测试治疗方法的第一步。来自疾病患者的诱导多能干细胞(iPS)已经用于此目的,因为它们可以分化成各种细胞。目前的研究调查了原发性癌症细胞和从iPS细胞分化的神经干细胞(NSCs)分泌的外泌体中的mtDNA畸变。原发性癌症细胞从手术切除的多形性胶质母细胞瘤(GBM)组织中分离,iPS细胞从对照和阿尔茨海默病(AD)受试者的B淋巴细胞中产生。我们检测到与GBM细胞分泌的外泌体相关的mtDNA畸变,但未检测到NSCs的畸变。这一结果表明,在不暴露于病理条件下,细胞可能不会分泌携带mtDNA畸变的外泌体。因此,当我们使用iPS细胞衍生的细胞作为体外疾病模型时,我们可能需要考虑这一事实。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exposure to a Pathological Condition May Be Required for the Cells to Secrete Exosomes Containing mtDNA Aberration
Exosomes, nanovesicles secreted by all cells, carry out intercellular communication by transmitting biologically active cargo comprising DNA, RNA, and proteins. These biomolecules reflect the status of their parent cells and can be altered by pathological conditions. Therefore, the researchers have been investigating differential sequences and quantities of DNA associated with exosomes as valuable biomarkers of diseases. Exosomes carry different types of DNA molecules, including genomic, cytoplasmic, and mitochondrial (mtDNA). The mtDNA aberrations are reported to be a hallmark of diseases involving oxidative stress, such as cancer and neurodegenerative diseases. Establishing robust in vitro models comprising appropriate cell lineages is the first step towards investigating disease-specific anomalies and testing therapeutics. Induced pluripotent stem (iPS) cells from patients with diseases have been used for this purpose since they can differentiate into various cells. The current study investigated mtDNA aberrations in exosomes secreted by primary cancer cells and neural stem cells (NSCs) differentiated from iPS cells. The primary cancer cells were isolated from surgically removed glioblastoma multiforme (GBM) tissue, and the iPS cells were produced from control and Alzheimer's disease (AD) subjects' B lymphocytes. We detected aberrations in mtDNA associated with exosomes secreted from GBM cells but not from the NSCs. This result indicates that the cells may not secrete exosomes carrying mtDNA aberration without exposure to a pathological condition. Thus, we may need to consider this fact when we use iPS cell-derived cells as an in vitro disease model.
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来源期刊
Journal of Nucleic Acids
Journal of Nucleic Acids BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
3.10
自引率
21.70%
发文量
5
审稿时长
12 weeks
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