Mechanically-sensitive miRNAs bias human mesenchymal stem cell fate via mTOR signalling.
Mechanically-sensitive miRNAs bias human mesenchymal stem cell fate via mTOR signalling.
复制标题
机械敏感的miRNA偏置通过MTOR信号传导人类间充质干细胞命运。
DOI：
10.1038/s41467-017-02486-0
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发表时间：
2018-01-17
影响因子：
16.6
通讯作者：
Cooper-White JJ
中科院分区：
文献类型：
--
作者：
Frith JE;Kusuma GD;Carthew J;Li F;Cloonan N;Gomez GA;Cooper-White JJ
机械转导是间充质干细胞（MSC）命运的强大驱动因素。在体外，基质力学的变化会引起间充质干细胞增殖、迁移和分化的变化。然而，当将MSCs纳入可注射的固有软水凝胶中时，这种对MSC反应的支配性极大地限制了我们将水凝胶的应用便利性与有效定向的MSC分化结合起来的能力，特别是在骨生成的情况下。在这里，我们确定了不同水凝胶硬度和RhoA活性的差异miRNA表达。我们表明miR-100-5p和miR-143-3p的调节可用于偏向MSC命运，并通过展示mTOR信号的收敛性提供机制见解。通过调节这些机械敏感的mirna，我们可以在柔软的3D水凝胶中促进成骨。本研究的结果提供了对MSC机械转导和分化调节机制的新理解，也是驱动MSC命运的新策略，并显著影响基于MSC的组织工程应用。间充质干细胞（MSC）的命运可以通过基质刚度进行机械调节，但这在3D水凝胶中很难控制。在这里，作者鉴定了mirna，这些mirna会根据底物硬度和RhoA信号而改变表达，并表明它们可以在3D软水凝胶中影响MSC的命运。
Mechanotransduction is a strong driver of mesenchymal stem cell (MSC) fate. In vitro, variations in matrix mechanics invoke changes in MSC proliferation, migration and differentiation. However, when incorporating MSCs within injectable, inherently soft hydrogels, this dominance over MSC response substantially limits our ability to couple the ease of application of hydrogels with efficiently directed MSC differentiation, especially in the case of bone generation. Here, we identify differential miRNA expression in response to varying hydrogel stiffness and RhoA activity. We show that modulation of miR-100-5p and miR-143-3p can be used to bias MSC fate and provide mechanistic insight by demonstrating convergence on mTOR signalling. By modulating these mechanosensitive miRNAs, we can enhance osteogenesis in a soft 3D hydrogel. The outcomes of this study provide new understanding of the mechanisms regulating MSC mechanotransduction and differentiation, but also a novel strategy with which to drive MSC fate and significantly impact MSC-based tissue-engineering applications. Mesenchymal stem cell (MSC) fate can be mechanically regulated by substrate stiffness but this is difficult to control in a 3D hydrogel. Here the authors identify miRNAs that change expression in response to substrate stiffness and RhoA signalling and show that they can bias MSC fate in a 3D soft hydrogel.
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影响因子：
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作者：
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通讯作者：
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