Transfer of microRNAs by embryonic stem cell microvesicles.
Transfer of microRNAs by embryonic stem cell microvesicles.
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DOI：
10.1371/journal.pone.0004722
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Farber DB
中科院分区：
文献类型：
--
作者：
Yuan A;Farber EL;Rapoport AL;Tejada D;Deniskin R;Akhmedov NB;Farber DB
微囊泡是由多种细胞类型释放到细胞外环境中的质膜衍生的囊泡。微泡最初以血小板为特征，是人体血浆的正常组成部分，在维持血液稳定中起重要作用。研究表明，微泡可以将蛋白质和RNA从一个细胞转移到另一个细胞，它们也被认为在细胞间通讯中发挥作用。我们表征了胚胎干细胞微泡的RNA和蛋白质含量，并表明它们可以被改造成携带外源表达的mRNA和蛋白质，如绿色荧光蛋白（GFP）。我们证明了这些工程微泡与其他胚胎干细胞对接并融合，转移它们的绿色荧光蛋白。此外，我们发现胚胎干细胞微泡含有丰富的microRNA，它们可以在体外将一小部分microRNA转移到小鼠胚胎成纤维细胞中。由于microrna是短的（21 - 24nt），自然存在的调节蛋白质翻译的rna，我们的发现开辟了一个有趣的可能性，即干细胞可以通过转移微泡中包含的microrna来改变邻近细胞中基因的表达。胚胎干细胞微泡可能是将mRNA、microrna、蛋白质和siRNA转移到细胞中的有用治疗工具，并且可能是干细胞龛内重要的信号传导介质。
Microvesicles are plasma membrane-derived vesicles released into the extracellular environment by a variety of cell types. Originally characterized from platelets, microvesicles are a normal constituent of human plasma, where they play an important role in maintaining hematostasis. Microvesicles have been shown to transfer proteins and RNA from cell to cell and they are also believed to play a role in intercellular communication. We characterized the RNA and protein content of embryonic stem cell microvesicles and show that they can be engineered to carry exogenously expressed mRNA and protein such as green fluorescent protein (GFP). We demonstrate that these engineered microvesicles dock and fuse with other embryonic stem cells, transferring their GFP. Additionally, we show that embryonic stem cells microvesicles contain abundant microRNA and that they can transfer a subset of microRNAs to mouse embryonic fibroblasts in vitro. Since microRNAs are short (21–24 nt), naturally occurring RNAs that regulate protein translation, our findings open up the intriguing possibility that stem cells can alter the expression of genes in neighboring cells by transferring microRNAs contained in microvesicles. Embryonic stem cell microvesicles may be useful therapeutic tools for transferring mRNA, microRNAs, protein, and siRNA to cells and may be important mediators of signaling within stem cell niches.
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影响因子：
56.9
作者：
Lagos-Quintana, M;Rauhut, R;Tuschl, T
通讯作者：
Tuschl, T
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通讯作者：
Marsh, Clay B.