Nat Commun:体积扩增和TRPV4活化调节三维微环境中的干细胞转化

2019-02-04 MedSci MedSci原创

对于在三维基质中培养的间充质干细胞(MSCs),基质重塑与增强的成骨分化相关。然而,将3D中的基质重塑与MSCs的骨生成联系起来的机制仍不清楚。在这里,我们发现粘弹性水凝胶中的MSCs在细胞扩散期间表现出体积膨胀,并且更大的体积膨胀与增强的骨生成相关。通过具有缓慢应力松弛或增加的渗透压的水凝胶限制膨胀减少了骨生成,而与细胞形态无关。相反,通过低渗压诱导的扩张加速了骨生成。体积扩增由TRPV4离子通

对于在三维基质中培养的间充质干细胞(MSCs),基质重塑与增强的成骨分化相关。然而,将3D中的基质重塑与MSCs的骨生成联系起来的机制仍不清楚。

在这里,我们发现粘弹性水凝胶中的MSCs在细胞扩散期间表现出体积膨胀,并且更大的体积膨胀与增强的骨生成相关。通过具有缓慢应力松弛或增加的渗透压的水凝胶限制膨胀减少了骨生成,而与细胞形态无关。相反,通过低渗压诱导的扩张加速了骨生成。体积扩增由TRPV4离子通道的激活介导,并且TRPV4激活和体积扩增之间的相互反馈控制RUNX2的核定位,但不控制YAP,以促进骨生成。

这项工作证明了细胞体积在调节3D培养中细胞命运中的作用,并将TRPV4鉴定为调节成骨分化的基质粘弹性的分子传感器。

原始出处:

Lee HP, Stowers R, Chaudhuri O. Volume expansion and TRPV4 activation regulate stem cell fate in three-dimensional microenvironments. Nat Commun. 2019 Jan 31;10(1):529. doi: 10.1038/s41467-019-08465-x.

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    2020-01-04 liuli5079

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    2019-11-19 liye789132251

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