The miR-590/Acvr2a/Terf1 Axis Regulates Telomere Elongation and Pluripotency of Mouse iPSCs.
The miR-590/Acvr2a/Terf1 Axis Regulates Telomere Elongation and Pluripotency of Mouse iPSCs.
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miR-590/Acvr2a/Terf1 轴调节小鼠 iPSC 的端粒伸长和多能性
DOI：
10.1016/j.stemcr.2018.05.008
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发表时间：
2018-07-10
影响因子：
5.9
通讯作者：
Kang J
中科院分区：
文献类型：
--
作者：
Liu Q;Wang G;Lyu Y;Bai M;Jiapaer Z;Jia W;Han T;Weng R;Yang Y;Yu Y;Kang J
在重编程过程中，端粒的重新延长对于获得多能性非常重要，并确保诱导的多潜能干细胞(IPSCs)的高质量，但其调节机制在很大程度上仍不清楚。我们的研究表明，完全重编程的成熟IPSCs或小鼠胚胎干细胞比IPSCs前表达更高水平的miR-590-3p和miR-590-5p。在前IPSCs中异位表达miR-590-3p或miR-590-5p可以改善端粒延长和多能性。激活素受体II A(Acvr2a)是miR-590的下游靶点，介导miR-590的功能。Acvr2a的下调促进了端粒的延长和多能性。MiR-590的过表达或激活素信号的抑制会增加端粒重复序列结合因子1(Terf1)的表达。与成熟的IPSCs相比，IPSCs前期的p-Smad2与Terf1启动子的结合增强。下调Terf1可阻断miR-590或shAcvr2a介导的对IPSCs前端粒延长和多能性的促进作用。本研究旨在阐明miR-590/Acvr2a/Terf1信号通路在调节前IPSCs端粒延长和多能性中的作用。MiR-590对IPSCs的端粒延长和多能性至关重要，miR-590可以靶向Acvr2a上调Terf1的表达miR-590/Acvr2a/Terf1轴调节IPSCs的延长和多能性在本文中，Kang及其同事阐明了miR-590/Acvr2a/Terf1信号通路在调节IPSCs的端粒延长和多能性中的关键功能和调控机制。这些发现不仅确定了miR-590/Acvr2a/Terf1轴对端粒延长和多能性的调节，还揭示了推动前IPSCs成熟的潜在机制。
During reprogramming, telomere re-elongation is important for pluripotency acquisition and ensures the high quality of induced pluripotent stem cells (iPSCs), but the regulatory mechanism remains largely unknown. Our study showed that fully reprogrammed mature iPSCs or mouse embryonic stem cells expressed higher levels of miR-590-3p and miR-590-5p than pre-iPSCs. Ectopic expression of either miR-590-3p or miR-590-5p in pre-iPSCs improved telomere elongation and pluripotency. Activin receptor II A (Acvr2a) is the downstream target and mediates the function of miR-590. Downregulation of Acvr2a promoted telomere elongation and pluripotency. Overexpression of miR-590 or inhibition of ACTIVIN signaling increased telomeric repeat binding factor 1 (Terf1) expression. The p-SMAD2 showed increased binding to the Terf1 promoter in pre-iPSCs compared with mature iPSCs. Downregulation of Terf1 blocked miR-590- or shAcvr2a-mediated promotion of telomere elongation and pluripotency in pre-iPSCs. This study elucidated the role of the miR-590/Acvr2a/Terf1 signaling pathway in modulating telomere elongation and pluripotency in pre-iPSCs. miR-590 is critical for telomere elongation and pluripotency of pre-iPSCs miR-590 can target Acvr2a to upregulate the expression of Terf1 miR-590/Acvr2a/Terf1 axis regulates the elongation and pluripotency of pre-iPSCs In this article, Kang and colleagues elucidate the critical function and regulatory mechanism of the miR-590/Acvr2a/Terf1 signaling pathway in modulating telomere elongation and pluripotency in pre-iPSCs. These findings not only determined the miR-590/Acvr2a/Terf1 axis on regulating both telomere elongation and pluripotency but also revealed an underlying mechanism pushing forward the maturation of the pre-iPSCs.
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