Proliferation of mouse embryonic stem cell progeny and the spontaneous contractile activity of cardiomyocytes are affected by microtopography.

Proliferation of mouse embryonic stem cell progeny and the spontaneous contractile activity of cardiomyocytes are affected by microtopography.
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DOI:
10.1002/dvdy.22030
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发表时间:
2009-08
影响因子:
2.5
通讯作者:
Russell, Brenda
Russell, Brenda
中科院分区:
生物学3区
文献类型:
--
作者:
Biehl, Jesse K.;Yamanaka, Satoshi;Desai, Tejal A.;Boheler, Kenneth R.;Russell, Brenda

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干细胞驻留和分化的生态位是一个复杂的物理化学微环境,调节细胞功能。使用在PDMS膜上创建的显微形貌,对来自小鼠胚胎干细胞的细胞后代研究了三维物理轮廓所起的作用。虽然分化标志物不受影响,但15 μm高的微突出物减弱了异种小鼠胚胎干细胞衍生后代的增殖,但5 μ m高的微突出物则没有。这种减少被Rho激酶和肌球蛋白轻链激酶抑制逆转,这降低了应力纤维的张力产生能力。与生长在平坦基底上的细胞相比,来自胚胎干细胞的纯化的心肌细胞也显示出显著的增殖钝化和增加的搏动速率。因此,干细胞衍生的后代的增殖似乎是通过在第三维的收缩力的张力产生的微观形貌调控。这些结果强调了地形线索在干细胞后代行为的调制中的重要性。
The niche in which stem cells reside and differentiate is a complex physico-chemical microenvironment that regulates cell function. The role played by three-dimensional physical contours was studied on cell progeny derived from mouse embryonic stem cells using microtopographies created on PDMS membranes. While markers of differentiation were not affected, the proliferation of heterogeneous mouse embryonic stem cell-derived progeny was attenuated by 15 μm-, but not 5 μm-high microprojections. This reduction was reversed by Rho kinase and myosin light chain kinase inhibition, which diminishes the tension generating ability of stress fibers. Purified cardiomyocytes derived from embryonic stem cells also showed significant blunting of proliferation and increased beating rates compared to cells grown on flat substrates. Thus, proliferation of stem cell-derived progeny appears to be regulated by microtopography through tension-generation of contractility in the third-dimension. These results emphasize the importance of topographic cues in the modulation of stem cell progeny behavior.
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