2013 Fiscal Year Final Research Report

Effect of mechanical stress on stemness of embryonic stem cells

Research Project

Project/Area Number	23650430
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Applied health science
Research Institution	The University of Tokyo
Principal Investigator	AKIMOTO Takayuki 東京大学, 医学(系)研究科(研究院), 講師 (00323460)
Project Period (FY)	2011 – 2013
Keywords	胚性幹細胞 / iPS細胞 / ES細胞 / メカノトランスダクション / 未分化性 / 物理刺激 / 力学刺激 / メカニカルストレス
Research Abstract	Mechanical strain has been reported to affect the proliferation/differentiation of many cell types. however, the effects of mechanotransduction on embryonic stem (ES) cells remains unknown. To investigate the effects of mechanical strain on ES cell fate, we examined the expression of Nanog as well as Nanog-associated intracellular signaling during uniaxial cyclic stretch. The mouse ES cell was plated onto elastic membranes, and we applied 10% strain at 0.16 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 mechanical strain attenuated this reduction of Nanog expression. On the other hand, the mechanical strain promoted PI3K-Akt signaling, which is reported as an upstream of Nanog transcription.These findings imply that mechanical force plays a role in regulating Nanog expression in ES cells through the actin cytoskeleton-PI3K-Akt signaling.