4 R# I$ V1 Q; [3 r1 P% c2 bNon-muscle myosin II regulates survival threshold of pluripotent stem cells + Y. @) Q* u4 W3 _2 C3 f! o) b6 d3 S2 S2 }" ^" ]4 D) \& L9 J: `
Andrea Walker, Hua Su,Mary Anne Conti,Nicole Harb,Robert S. Adelstein& Noboru Sato : L! Q! F$ p' O/ B$ v ; h! ]! g% }- x I0 R: IHuman pluripotent stem (hPS) cells such as human embryonic stem (hES) and induced pluripotent stem (hiPS) cells are vulnerable under single cell conditions, which hampers practical applications; yet, the mechanisms underlying this cell death remain elusive. In this paper, we demonstrate that treatment with a specific inhibitor of non-muscle myosin II (NMII), blebbistatin, enhances the survival of hPS cells under clonal density and suspension conditions, and, in combination with a synthetic matrix, supports a fully defined environment for self-renewal. Consistent with this, genetically engineered mouse embryonic stem cells lacking an isoform of NMII heavy chain (NMHCII), or hES cells expressing a short hairpin RNA to knock down NMHCII, show greater viability than controls. Moreover, NMII inhibition increases the expression of self-renewal regulators Oct3/4 and Nanog, suggesting a mechanistic connection between NMII and self-renewal. These results underscore the importance of the molecular motor, NMII, as a novel target for chemically engineering the survival and self-renewal of hPS cells作者: zhaoyan1983 时间: 2010-9-9 16:47