Exogenous Nanog alleviates but is insufficient to reverse embryonic stem cells differentiation induced by PI3K signaling inhibition

J Cell Biochem. 2009 Apr 15;106(6):1041-7. doi: 10.1002/jcb.22082.

Abstract

PI3K signaling pathway plays a significant role in embryonic stem cells (ES cells) self-renewal. Overexpression of Nanog maintains mouse ES cells pluripotency independent of leukemia inhibitory factor (LIF). However, little is known about the effect of PI3K signaling pathway on ES cells with Nanog overexpression. Our experiments aimed to explore the relationship between PI3K signaling pathway and Nanog expression in ES cells. We observed the effect of LY294002, a specific inhibitor of PI3K pathway, on wild-type J1 cells and Nanog overexpressing (Ex-Nanog) J1 cells in the presence or absence of LIF. With LY294002 treatment, both of them lost their ES features even in the presence of LIF. But the differentiation induced by LY294002 on Ex-Nanog J1 cells was slighter lower than that on wild-type J1 cells. These results indicate that inhibition of PI3K pathway induces mouse ES cells differentiation. Exogenous Nanog sustains mouse ES cells pluripotency independent of LIF, and alleviates the differentiation induced by LY294002. But it is insufficient to totally reverse the differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Chromones / metabolism
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / physiology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Leukemia Inhibitory Factor / pharmacology
  • Mice
  • Morpholines / metabolism
  • Nanog Homeobox Protein
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / physiology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / physiology*

Substances

  • Chromones
  • Homeodomain Proteins
  • Leukemia Inhibitory Factor
  • Morpholines
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • Phosphoinositide-3 Kinase Inhibitors
  • Recombinant Fusion Proteins
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one