Beta-catenin signaling contributes to stemness and regulates early differentiation in murine embryonic stem cells

FEBS Lett. 2007 Nov 13;581(27):5247-54. doi: 10.1016/j.febslet.2007.10.012. Epub 2007 Oct 15.

Abstract

ES cells can self-renew while preserving pluripotency and are able to differentiate into many cell types. In both processes, different signal transduction pathways are implicated, including the Wnt/beta-catenin pathway, which we here further analyzed. We found that a loss of beta-catenin in ES cells leads to altered expression of stem cell marker genes. TCF/beta-catenin reporter gene assays indicate that undifferentiated murine ES cells are capable of reacting to LiCl and Wnt3a but not Wnt5a stimulation, but have low endogenous TCF/beta-catenin activity. Oct-3/4, nanog and Wnt11 were able to repress TCF/beta-catenin transcriptional activity. During differentiation, activation of the Wnt/beta-catenin pathway influences formation of mesoderm and cardiomyocytes in a time and dose dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / metabolism*
  • Fetal Proteins / genetics
  • Lithium Chloride / pharmacology
  • Mice
  • Mice, Knockout
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • T-Box Domain Proteins / genetics
  • TCF Transcription Factors / metabolism
  • Transcription Factors / metabolism
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism
  • Wnt Proteins / pharmacology
  • Wnt3 Protein
  • Wnt3A Protein
  • beta Catenin / deficiency
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • CTNNB1 protein, mouse
  • Fetal Proteins
  • Recombinant Proteins
  • T-Box Domain Proteins
  • TCF Transcription Factors
  • Transcription Factors
  • Wnt Proteins
  • Wnt3 Protein
  • Wnt3A Protein
  • Wnt3a protein, mouse
  • beta Catenin
  • Brachyury protein
  • Lithium Chloride