Topal Tuğba, Kim Byoung Choul, Villa-Diaz Luis G, Deng Cheri X, Takayama Shuichi, Krebsbach Paul H
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
Integr Biol (Camb). 2019 Feb 1;11(2):41-52. doi: 10.1093/intbio/zyz003.
Human embryonic stem cells subjected to a one-time uniaxial stretch for as short as 30-min on a flexible substrate coated with Matrigel experienced rapid and irreversible nuclear-to-cytoplasmic translocation of NANOG and OCT4, but not Sox2. Translocations were directed by intracellular transmission of biophysical signals from cell surface integrins to nuclear CRM1 and were independent of exogenous soluble factors. On E-CADHERIN-coated substrates, presumably with minimal integrin engagement, mechanical strain-induced rapid nuclear-to-cytoplasmic translocation of the three transcription factors. These findings might provide fundamental insights into early developmental processes and may facilitate mechanotransduction-mediated bioengineering approaches to influencing stem cell fate determination.
在涂有基质胶的柔性底物上，对人类胚胎干细胞进行单次30分钟的单轴拉伸，NANOG和OCT4会发生快速且不可逆的核至细胞质易位，但Sox2不会。这种易位是由生物物理信号从细胞表面整合素向细胞核CRM1的细胞内传递所引导的，并且独立于外源性可溶性因子。在涂有E-钙黏蛋白的底物上，推测整合素参与最少，机械应变会诱导这三种转录因子发生快速的核至细胞质易位。这些发现可能为早期发育过程提供基本见解，并可能促进机械转导介导的生物工程方法来影响干细胞命运的决定。
