Non-muscle myosin II regulates survival threshold of pluripotent stem cells

Nat Commun. 2010 Sep 7;1:71. doi: 10.1038/ncomms1074.

Abstract

Human 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / genetics
  • Cell Survival / physiology
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / metabolism
  • Genetic Vectors / genetics
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Humans
  • In Situ Nick-End Labeling
  • Karyotyping
  • Lentivirus / genetics
  • Mice
  • Myosin Type II / genetics
  • Myosin Type II / metabolism*
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / drug effects
  • Pluripotent Stem Cells / metabolism*
  • RNA, Small Interfering / genetics

Substances

  • Heterocyclic Compounds, 4 or More Rings
  • RNA, Small Interfering
  • blebbistatin
  • Myosin Type II