Contribution of the PI3K/Akt/PKB signal pathway to maintenance of self-renewal in human embryonic stem cells

FEBS Lett. 2005 Jan 17;579(2):534-40. doi: 10.1016/j.febslet.2004.12.024.

Abstract

Although basic fibroblast growth factor (FGF2) is generally included in the media for maintenance of human embryonic stem cells (hESCs), the action of FGF2 in these cells has not been well defined. Here, we determined the roles of FGF2 in maintaining hESC self-renewal. Withdrawal of FGF2 from the media led to acquisition of typical differentiated characteristics in hESCs. In the presence of FGF2, which is normally required for proliferation in an undifferentiated state, inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt/PKB signal stimulated differentiation and attenuated the expression of extracellular matrix (ECM) molecules. We suggest that FGF2 maintains hESC self-renewal by supporting stable expression of ECM molecules through activation of the PI3K/Akt/PKB pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • 3-Phosphoinositide-Dependent Protein Kinases
  • Cell Differentiation / physiology
  • Cell Proliferation
  • Chromones / pharmacology
  • Embryo, Mammalian / cytology*
  • Extracellular Matrix Proteins / metabolism
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibroblast Growth Factor 2 / physiology*
  • Humans
  • Morpholines / pharmacology
  • Phosphatidylinositol 3-Kinases / physiology
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / physiology
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-akt
  • Receptors, Laminin / physiology
  • Signal Transduction*
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / enzymology*

Substances

  • Chromones
  • Extracellular Matrix Proteins
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Receptors, Laminin
  • Fibroblast Growth Factor 2
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • 3-Phosphoinositide-Dependent Protein Kinases
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt