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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Taylor, Russell J. Moon, Randall T. Mcdonald, Circe E. Goodson, Jamie M. Adams, Allison M. Potter, Jennifer C. Biechele, Travis L. Berndt, Jason D. Davidson, Kathryn C. |
| Description | Author Affiliation: Davidson KC ( Department of Pharmacology, Howard Hughes Medical Institute, and the Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA.); |
| Abstract | Signal transduction pathways play diverse, context-dependent roles in vertebrate development. In studies of human embryonic stem cells (hESCs), conflicting reports claim Wnt/ß-catenin signaling promotes either self-renewal or differentiation. We use a sensitive reporter to establish that Wnt/ß-catenin signaling is not active during hESC self-renewal. Inhibiting this pathway over multiple passages has no detrimental effect on hESC maintenance, whereas activating signaling results in loss of self-renewal and induction of mesoderm lineage genes. Following exposure to pathway agonists, hESCs exhibit a delay in activation of ß-catenin signaling, which led us to postulate that Wnt/ß-catenin signaling is actively repressed during self-renewal. In support of this hypothesis, we demonstrate that OCT4 represses ß-catenin signaling during self-renewal and that targeted knockdown of OCT4 activates ß-catenin signaling in hESCs. Using a fluorescent reporter of ß-catenin signaling in live hESCs, we observe that the reporter is activated in a very heterogeneous manner in response to stimulation with Wnt ligand. Sorting cells on the basis of their fluorescence reveals that hESCs with elevated ß-catenin signaling express higher levels of differentiation markers. Together these data support a dominant role for Wnt/ß-catenin signaling in the differentiation rather than self-renewal of hESCs. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 12 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-03-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Embryonic Stem Cells Cytology Octamer Transcription Factor-3 Metabolism Wnt Proteins Beta Catenin Animals Cell Differentiation Cell Lineage Cell Proliferation Coculture Techniques Genes, Reporter Mice Models, Biological Signal Transduction Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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