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Y-RNA subtype ratios in plasma extracellular vesicles are cell type- specific and are candidate biomarkers for inflammatory diseases.
Journal of Extracellular Vesicles ( IF 16.0 ) Pub Date : 2020-05-26 , DOI: 10.1080/20013078.2020.1764213
Tom A P Driedonks 1 , Sanne Mol 1, 2 , Sanne de Bruin 3 , Anna-Linda Peters 4 , Xiaogang Zhang 1 , Marthe F S Lindenbergh 1 , Boukje M Beuger 5 , Anne-Marieke D van Stalborch 6 , Thom Spaan 7 , Esther C de Jong 2 , Erhard van der Vries 7 , Coert Margadant 6 , Robin van Bruggen 5 , Alexander P J Vlaar 3 , Tom Groot Kormelink 2 , Esther N M Nolte-'t Hoen 1
Affiliation  

Major efforts are made to characterize the presence of microRNA (miRNA) and messenger RNA in blood plasma to discover novel disease-associated biomarkers. MiRNAs in plasma are associated to several types of macromolecular structures, including extracellular vesicles (EV), lipoprotein particles (LPP) and ribonucleoprotein particles (RNP). RNAs in these complexes are recovered at variable efficiency by commonly used EV- and RNA isolation methods, which causes biases and inconsistencies in miRNA quantitation. Besides miRNAs, various other non-coding RNA species are contained in EV and present within the pool of plasma extracellular RNA. Members of the Y-RNA family have been detected in EV from various cell types and are among the most abundant non-coding RNA types in plasma. We previously showed that shuttling of full-length Y-RNA into EV released by immune cells is modulated by microbial stimulation. This indicated that Y-RNAs could contribute to the functional properties of EV in immune cell communication and that EV-associated Y-RNAs could have biomarker potential in immune-related diseases. Here, we investigated which macromolecular structures in plasma contain full length Y-RNA and whether the levels of three Y-RNA subtypes in plasma (Y1, Y3 and Y4) change during systemic inflammation. Our data indicate that the majority of full length Y-RNA in plasma is stably associated to EV. Moreover, we discovered that EV from different blood-related cell types contain cell-type-specific Y-RNA subtype ratios. Using a human model for systemic inflammation, we show that the neutrophil-specific Y4/Y3 ratios and PBMC-specific Y3/Y1 ratios were significantly altered after induction of inflammation. The plasma Y-RNA ratios strongly correlated with the number and type of immune cells during systemic inflammation. Cell-type-specific "Y-RNA signatures" in plasma EV can be determined without prior enrichment for EV, and may be further explored as simple and fast test for diagnosis of inflammatory responses or other immune-related diseases.

中文翻译:

血浆细胞外囊泡中的 Y-RNA 亚型比率具有细胞类型特异性,是炎症性疾病的候选生物标志物。

人们主要致力于表征血浆中 microRNA (miRNA) 和信使 RNA 的存在,以发现新的疾病相关生物标志物。血浆中的 miRNA 与多种类型的大分子结构相关,包括细胞外囊泡 (EV)、脂蛋白颗粒 (LPP) 和核糖核蛋白颗粒 (RNP)。这些复合物中的 RNA 通过常用的 EV 和 RNA 分离方法以不同的效率回收,这会导致 miRNA 定量的偏差和不一致。除了 miRNA 之外,EV 中还包含各种其他非编码 RNA 并存在于血浆细胞外 RNA 库中。Y-RNA 家族成员已在多种细胞类型的 EV 中检测到,并且是血浆中最丰富的非编码 RNA 类型之一。我们之前表明,全长 Y-RNA 穿梭到免疫细胞释放的 EV 中是受到微生物刺激的调节。这表明 Y-RNA 可能有助于 EV 在免疫细胞通讯中的功能特性,并且 EV 相关 Y-RNA 可能在免疫相关疾病中具有生物标志物潜力。在这里,我们研究了血浆中哪些大分子结构含有全长 Y-RNA,以及血浆中三种 Y-RNA 亚型(Y1、Y3 和 Y4)的水平在全身炎症过程中是否发生变化。我们的数据表明血浆中大部分全长 Y-RNA 与 EV 稳定相关。此外,我们发现来自不同血液相关细胞类型的 EV 包含细胞类型特异性的 Y-RNA 亚型比率。使用人体全身炎症模型,我们发现中性粒细胞特异性 Y4/Y3 比率和 PBMC 特异性 Y3/Y1 比率在诱导炎症后显着改变。血浆 Y-RNA 比率与全身炎症期间免疫细胞的数量和类型密切相关。无需事先对 EV 进行富集即可确定血浆 EV 中细胞类型特异性的“Y-RNA 特征”,并且可以进一步探索作为诊断炎症反应或其他免疫相关疾病的简单快速测试。
更新日期:2020-05-26
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