Role of the MicroRNA-17-92 Cluster in the Endothelial Differentiation of Stem Cells

Role of the MicroRNA-17-92 Cluster in the Endothelial Differentiation of Stem Cells
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DOI:
10.1159/000339429
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发表时间:
2012-01-01
影响因子:
1.7
通讯作者:
Dimmeler, Stefanie
Dimmeler, Stefanie
中科院分区:
医学4区
文献类型:
--
作者:
Treguer, Karine;Heinrich, Eva-Marie;Dimmeler, Stefanie

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MicroRNA (miR) 是一种小型非编码 RNA,最近成为基因表达的有效调节因子。 miR-17-92 簇的成员已被证明可以控制内皮细胞功能和新血管形成;然而,该簇在内皮细胞谱系定型中的调节和功能尚未被探索。该项目旨在测试 miR-17-92 簇在内皮分化过程中的作用。我们证明,在诱导小鼠胚胎干细胞或诱导多能干细胞的内皮细胞分化时,miR-17、miR-18、miR-19和miR-20增加。相反,miR-92a 和初级 miR-17-92 转录本下调。胆固醇修饰的antagomir对簇中每个个体miR的抑制不影响内皮标记基因表达。此外,所有antagomir的组合没有效果。这些发现表明,尽管miR-17-92簇调节血管完整性和血管生成,但没有一个成员对多能干细胞的内皮分化产生显着影响。版权所有 (C) 2012 S. Karger AG,巴塞尔
MicroRNAs (miRs) are small non-coding RNAs that recently emerged as potent regulators of gene expression. The members of the miR-17-92 cluster have been shown to control endothelial cell functions and neovascularization; however, the regulation and function of the cluster in endothelial cell lineage commitment has not been explored. This project aimed to test the role of the miR-17-92 cluster during endothelial differentiation. We demonstrate that miR-17, miR-18, miR-19 and miR-20 are increased upon the induction of endothelial cell differentiation of murine embryonic stem cells or induced pluripotent stem cells. In contrast, miR-92a and the primary miR-17-92 transcript were downregulated. The inhibition of each individual miR of the cluster by cholesterol-modified antagomirs did not affect endothelial marker gene expression. Moreover, the combination of all antagomirs had no effect. These findings illustrate that although the miR-17-92 cluster regulates vascular integrity and angiogenesis, none of the members has a significant impact on the endothelial differentiation of pluripotent stem cells. Copyright (C) 2012 S. Karger AG, Basel