Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs.
Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs.
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DOI：
10.1371/journal.pone.0011803
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发表时间：
2010-07-27
期刊：
影响因子：
3.7
通讯作者：
Camussi G
中科院分区：
文献类型：
--
作者：
Collino F;Deregibus MC;Bruno S;Sterpone L;Aghemo G;Viltono L;Tetta C;Camussi G
细胞来源的微泡（MV）被描述为细胞间通信的新机制。目标细胞内部化后的MV可以传递遗传信息。人类骨髓衍生的间充质干细胞（MSC）和肝脏常驻干细胞（HLSC）被证明可以释放MVS式班车功能性mRNA。本研究的目的是评估源自MSC和HLSC的MV是否包含选定的微RNA（miRNA）。
从MSC和HLSC中分离MV。评估了参与RNA交通和稳定的选定核糖核蛋白的MV中的存在。我们观察到MVS包含在核和应力颗粒中表达的TIA，TIAR和HUR多功能蛋白，STAU1和2涉及mRNA的转运和稳定性，以及参与miRNA运输和加工的传输和稳定性。从MVS中提取的RNA和原始细胞由实时PCR分为365个已知的人类成熟miRNA。 miRNA的分层聚类和相似性分析显示，MV和细胞中有41个共表达miRNA。 MV释放后，一些miRNA积聚在MV中，在细胞中不存在。其他人则保留在细胞内，而不是在MV中分泌。对预测和验证靶标的基因本体分析表明，细胞和MV中高表达的miRNA可能与多器官发育，细胞存活和分化有关。 MVS穿梭的一些选定的miRNA也与免疫系统调节有关。 MV掺入后，将MV中高表达的miRNA转移到靶细胞中。
这项研究表明，MVS含有参与RNA细胞内流量和选定miRNA模式的核糖核蛋白，表明MVS中RNA分区化的动态调节。将MV高表达的miRNA转移到靶细胞上的观察结果，它提高了干细胞的生物学作用至少部分取决于MV-Shuttled miRNA。这项研究产生的数据刺激了对人类干细胞生物学作用的预测靶基因和途径进行进一步的功能研究。
Cell-derived microvesicles (MVs) have been described as a new mechanism of cell-to-cell communication. MVs after internalization within target cells may deliver genetic information. Human bone marrow derived mesenchymal stem cells (MSCs) and liver resident stem cells (HLSCs) were shown to release MVs shuttling functional mRNAs. The aim of the present study was to evaluate whether MVs derived from MSCs and HLSCs contained selected micro-RNAs (miRNAs). MVs were isolated from MSCs and HLSCs. The presence in MVs of selected ribonucleoproteins involved in the traffic and stabilization of RNA was evaluated. We observed that MVs contained TIA, TIAR and HuR multifunctional proteins expressed in nuclei and stress granules, Stau1 and 2 implicated in the transport and stability of mRNA and Ago2 involved in miRNA transport and processing. RNA extracted from MVs and cells of origin was profiled for 365 known human mature miRNAs by real time PCR. Hierarchical clustering and similarity analysis of miRNAs showed 41 co-expressed miRNAs in MVs and cells. Some miRNAs were accumulated within MVs and absent in the cells after MV release; others were retained within the cells and not secreted in MVs. Gene ontology analysis of predicted and validated targets showed that the high expressed miRNAs in cells and MVs could be involved in multi-organ development, cell survival and differentiation. Few selected miRNAs shuttled by MVs were also associated with the immune system regulation. The highly expressed miRNAs in MVs were transferred to target cells after MV incorporation. This study demonstrated that MVs contained ribonucleoproteins involved in the intracellular traffic of RNA and selected pattern of miRNAs, suggesting a dynamic regulation of RNA compartmentalization in MVs. The observation that MV-highly expressed miRNAs were transferred to target cells, rises the possibility that the biological effect of stem cells may, at least in part, depend on MV-shuttled miRNAs. Data generated from this study, stimulate further functional investigations on the predicted target genes and pathways involved in the biological effect of human adult stem cells.
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影响因子：
20.3
作者：
Deregibus, Maria Chiara;Cantaluppi, Vincenzo;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
64.5
作者：
Ballas, N;Grunseich, C;Mandel, G
通讯作者：
Mandel, G
影响因子：
11.5
作者：
Bandres, Eva;Bitarte, Nerea;Garcia-Foncillas, Jesus
通讯作者：
Garcia-Foncillas, Jesus
DOI：
10.1073/pnas.0712312105
发表时间：
2008-03-04
影响因子：
11.1
作者：
Dore, Louis C.;Amigo, Julio D.;Weiss, Mitchell J.
通讯作者：
Weiss, Mitchell J.
DOI：
10.1073/pnas.0703037104
发表时间：
2007-09-25
影响因子：
11.1
作者：
Greco, Steven J.;Rameshwar, Pranela
通讯作者：
Rameshwar, Pranela