Division of Regenerative Medical Engineering, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan.
Exp Cell Res. 2012 Aug 15;318(14):1726-32. doi: 10.1016/j.yexcr.2012.05.021. Epub 2012 Jun 6.
Mechanical strain has been reported to affect the proliferation/differentiation of many cell types; however, the effects of mechanotransduction on self-renewal as well as pluripotency of embryonic stem (ES) cells remains unknown. To investigate the effects of mechanical strain on mouse ES cell fate, we examined the expression of Nanog, which is an essential regulator of self-renewal and pluripotency as well as Nanog-associated intracellular signaling during uniaxial cyclic mechanical strain. The mouse ES cell line, CCE was plated onto elastic membranes, and we applied 10% strain at 0.17 Hz. The expression of Nanog was reduced during ES cell differentiation in response to the withdrawal of leukemia inhibitory factor (LIF); however, two days of cyclic mechanical strain attenuated this reduction of Nanog expression. On the other hand, the cyclic mechanical strain promoted PI3K-Akt signaling, which is reported as an upstream of Nanog transcription. The cyclic mechanical strain-induced Akt phosphorylation was blunted by the PI3K inhibitor wortmannin. Furthermore, cytochalasin D, an inhibitor of actin polymerization, also inhibited the mechanical strain-induced increase in phospho-Akt. These findings imply that mechanical force plays a role in regulating Nanog expression in ES cells through the actin cytoskeleton-PI3K-Akt signaling.
机械应变已被报道影响许多细胞类型的增殖/分化；然而，机械转导对胚胎干细胞（ES）细胞自我更新以及多能性的影响尚不清楚。为了研究机械应变对小鼠 ES 细胞命运的影响，我们研究了 Nanog 的表达，Nanog 是自我更新和多能性的重要调节因子，也是机械应变过程中与 Nanog 相关的细胞内信号。将小鼠 ES 细胞系 CCE 接种到弹性膜上，并以 0.17 Hz 的频率施加 10%的应变。在响应白血病抑制因子（LIF）的撤去时，ES 细胞分化过程中 Nanog 的表达减少；然而，两天的周期性机械应变减弱了这种 Nanog 表达的减少。另一方面，周期性机械应变促进了 PI3K-Akt 信号的传递，这被报道为 Nanog 转录的上游。PI3K 抑制剂wortmannin 可减弱周期性机械应变诱导的 Akt 磷酸化。此外，肌动蛋白聚合抑制剂细胞松弛素 D 也抑制了机械应变诱导的磷酸化 Akt 的增加。这些发现表明，机械力通过肌动蛋白细胞骨架-PI3K-Akt 信号通路在 ES 细胞中调节 Nanog 的表达。
