Beta-catenin signaling contributes to stemness and regulates early differentiation in murine embryonic stem cells.
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.
Anton
Roman
R
Institute for Biochemistry and Molecular Biology, Ulm University, D-89069 Ulm, Germany.
Kestler
Hans A
HA
Kühl
Michael
M
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005326:Fetal Proteins / Q000235:genetics; D018021:Lithium Chloride / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics; D051820:TCF Transcription Factors / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000098908:Brachyury Protein
D005326:Fetal Proteins; D018021:Lithium Chloride; D011994:Recombinant Proteins; D020825:T-Box Domain Proteins; D051820:TCF Transcription Factors; D014157:Transcription Factors; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin; D000098908:Brachyury Protein; C495267:CTNNB1 protein, mouse; C555511:Wnt3a protein, mouse