3D microniches reveal the importance of cell size and shape.

3D microniches reveal the importance of cell size and shape.
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DOI:
10.1038/s41467-017-02163-2
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发表时间:
2017-12-06
影响因子:
16.6
通讯作者:
Huck WTS
Huck WTS
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bao M;Xie J;Piruska A;Huck WTS

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几何线索已被证明可以改变2D底物上的基因表达和分化。然而,很少有人知道几何线索如何影响细胞功能的3D。缺乏理解的一个主要原因是在复杂的3D环境中控制细胞几何形状和长时间培养的困难。在这里,我们提出了一种稳健的方法来控制具有一系列不同几何形状(例如,圆柱体、三棱柱、立方体和长方体)。我们发现,肌动蛋白丝,粘着斑,核形状,雅普/TAZ定位,细胞收缩性,组蛋白去乙酰化酶3的核积累,和谱系选择都是敏感的细胞体积。我们的3D microniches使生物物理线索对细胞命运的影响的基础研究,并在调查多细胞架构如何在几何定义良好的3D空间内组织有潜在的应用。关于几何线索如何影响3D环境中的细胞功能和基因表达,我们知之甚少。在这里,作者使用不同几何形状的微区来控制细胞体积和形状,并通过扩展细胞表型和谱系。
Geometrical cues have been shown to alter gene expression and differentiation on 2D substrates. However, little is known about how geometrical cues affect cell function in 3D. One major reason for this lack of understanding is rooted in the difficulties of controlling cell geometry in a complex 3D setting and for long periods of culture. Here, we present a robust method to control cell volume and shape of individual human mesenchymal stem cells (hMSCs) inside 3D microniches with a range of different geometries (e.g., cylinder, triangular prism, cubic, and cuboid). We find that the actin filaments, focal adhesions, nuclear shape, YAP/TAZ localization, cell contractility, nuclear accumulation of histone deacetylase 3, and lineage selection are all sensitive to cell volume. Our 3D microniches enable fundamental studies on the impact of biophysical cues on cell fate, and have potential applications in investigating how multicellular architectures organize within geometrically well-defined 3D spaces. Little is known about how geometric cues affect cell function and gene expression in 3D settings. Here the authors use microniches of different geometries to control cell volume and shape, and by extension cell phenotype and lineage.
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