Immune stimuli shape the small non-coding transcriptome of extracellular vesicles released by dendritic cells.
Immune stimuli shape the small non-coding transcriptome of extracellular vesicles released by dendritic cells.
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DOI：
10.1007/s00018-018-2842-8
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Nolte-'t Hoen ENM
中科院分区：
文献类型：
--
作者：
Driedonks TAP;van der Grein SG;Ariyurek Y;Buermans HPJ;Jekel H;Chow FWN;Wauben MHM;Buck AH;'t Hoen PAC;Nolte-'t Hoen ENM
细胞外纳米囊泡(EV)的释放和摄取是一种高度保守的细胞间通讯方式。EV的分子组成，从而它们对靶细胞的信号功能，受到细胞激活和分化刺激的调节。EV被视为细胞的快照，因此作为疾病的生物标志物而备受关注。虽然对EV相关RNA的研究主要集中在microRNAs上，但EV的转录组由多类具有潜在基因调控功能的非编码小RNA组成。目前尚不清楚施加在细胞上的环境信号是否会在广泛的EV相关RNA类别中诱导特定的变化。在这里，我们研究了施加在原始树突状细胞上的免疫激活或抑制刺激是否影响通过EV释放各种小的非编码RNA。用RNA测序和RT-qPCR方法分析不含核糖核蛋白颗粒的高纯度EV群体的小RNA转录本。来自树突状细胞的EV的miRNA、snoRNA和Y-RNA含量发生了免疫刺激特异性的变化，而tRNA和SnRNA水平受到的影响要小得多。EV-RNA含量的变化只有一部分反映了细胞RNA的变化，这敦促在将EV解释为细胞快照时要谨慎。通过对从高纯度EV中获得的RNA的综合分析，我们证明了多个RNA类别有助于通过EV传递遗传信息。多个显示细胞刺激依赖与EV相关的RNA类别的鉴定是揭开这些EV-RNAs功能和生物标志物潜力的前奏。本文的在线版本(10.1007/s000180182842-8)包含补充材料，可供授权用户使用。
The release and uptake of nano-sized extracellular vesicles (EV) is a highly conserved means of intercellular communication. The molecular composition of EV, and thereby their signaling function to target cells, is regulated by cellular activation and differentiation stimuli. EV are regarded as snapshots of cells and are, therefore, in the limelight as biomarkers for disease. Although research on EV-associated RNA has predominantly focused on microRNAs, the transcriptome of EV consists of multiple classes of small non-coding RNAs with potential gene-regulatory functions. It is not known whether environmental cues imposed on cells induce specific changes in a broad range of EV-associated RNA classes. Here, we investigated whether immune-activating or -suppressing stimuli imposed on primary dendritic cells affected the release of various small non-coding RNAs via EV. The small RNA transcriptomes of highly pure EV populations free from ribonucleoprotein particles were analyzed by RNA sequencing and RT-qPCR. Immune stimulus-specific changes were found in the miRNA, snoRNA, and Y-RNA content of EV from dendritic cells, whereas tRNA and snRNA levels were much less affected. Only part of the changes in EV-RNA content reflected changes in cellular RNA, which urges caution in interpreting EV as snapshots of cells. By comprehensive analysis of RNA obtained from highly purified EV, we demonstrate that multiple RNA classes contribute to genetic messages conveyed via EV. The identification of multiple RNA classes that display cell stimulation-dependent association with EV is the prelude to unraveling the function and biomarker potential of these EV-RNAs. The online version of this article (10.1007/s00018-018-2842-8) contains supplementary material, which is available to authorized users.
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DOI：
10.4137/bic.s20764
发表时间：
2014
期刊：
Biomarkers in cancer
影响因子：
--
作者：
Dhahbi JM;Spindler SR;Atamna H;Boffelli D;Martin DI
通讯作者：
Martin DI
影响因子：
30.5
作者：
Agudo, Judith;Ruzo, Albert;Tung, Navpreet;Salmon, Helene;Leboeuf, Marylene;Hashimoto, Daigo;Becker, Christian;Garrett-Sinha, Lee-Ann;Baccarini, Alessia;Merad, Miriam;Brown, Brian D.
通讯作者：
Brown, Brian D.
影响因子：
3.7
作者：
Fiskaa T;Knutsen E;Nikolaisen MA;Jørgensen TE;Johansen SD;Perander M;Seternes OM
通讯作者：
Seternes OM
影响因子：
9.2
作者：
Chen, XG;Smith, JD;Wolin, SL
通讯作者：
Wolin, SL
影响因子：
20.1
作者：
Kaudewitz D;Skroblin P;Bender LH;Barwari T;Willeit P;Pechlaner R;Sunderland NP;Willeit K;Morton AC;Armstrong PC;Chan MV;Lu R;Yin X;Gracio F;Dudek K;Langley SR;Zampetaki A;de Rinaldis E;Ye S;Warner TD;Saxena A;Kiechl S;Storey RF;Mayr M
通讯作者：
Mayr M