| Signaling network crosstalk in human pluripotent cells: a Smad2/3-regulated switch that controls the balance between self-renewal and differentiation. | |
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MedLine Citation:
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PMID: 22385658 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A general mechanism for how intracellular signaling pathways in human pluripotent cells are coordinated and how they maintain self-renewal remain to be elucidated. In this report, we describe a signaling mechanism where PI3K/Akt activity maintains self-renewal by restraining prodifferentiation signaling through suppression of the Raf/Mek/Erk and canonical Wnt signaling pathways. When active, PI3K/Akt establishes conditions where Activin A/Smad2,3 performs a pro-self-renewal function by activating target genes, including Nanog. When PI3K/Akt signaling is low, Wnt effectors are activated and function in conjunction with Smad2,3 to promote differentiation. The switch in Smad2,3 activity after inactivation of PI3K/Akt requires the activation of canonical Wnt signaling by Erk, which targets Gsk3β. In sum, we define a signaling framework that converges on Smad2,3 and determines its ability to regulate the balance between alternative cell states. This signaling paradigm has far-reaching implications for cell fate decisions during early embryonic development. |
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Authors:
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Amar M Singh; David Reynolds; Timothy Cliff; Satoshi Ohtsuka; Alexa L Mattheyses; Yuhua Sun; Laura Menendez; Michael Kulik; Stephen Dalton |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Cell stem cell Volume: 10 ISSN: 1875-9777 ISO Abbreviation: Cell Stem Cell Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-03-05 Completed Date: 2012-08-03 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 101311472 Medline TA: Cell Stem Cell Country: United States |
Other Details:
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Languages: eng Pagination: 312-26 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Biochemistry and Molecular Biology, Paul D. Coverdell Center for Biomedical and Health Sciences, The University of Georgia, Athens, GA 30602, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Differentiation* Cells, Cultured Genes, Switch / physiology* Humans Immunoblotting Models, Biological Pluripotent Stem Cells / physiology* Polymerase Chain Reaction Regeneration* Signal Transduction* Smad2 Protein / metabolism, physiology* Smad3 Protein / metabolism, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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GM75334/GM/NIGMS NIH HHS; HD049647/HD/NICHD NIH HHS; P01 GM085354-01/GM/NIGMS NIH HHS; P01 GM085354-02/GM/NIGMS NIH HHS; P01 GM085354-02S1/GM/NIGMS NIH HHS; P01 GM085354-03/GM/NIGMS NIH HHS; P01 GM085354-04/GM/NIGMS NIH HHS; P01 GM085354-05/GM/NIGMS NIH HHS; R01 HD049647-01A1/HD/NICHD NIH HHS; R01 HD049647-02/HD/NICHD NIH HHS; R01 HD049647-03/HD/NICHD NIH HHS; R01 HD049647-04/HD/NICHD NIH HHS; R01 HD049647-05/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/SMAD2 protein, human; 0/Smad2 Protein; 0/Smad3 Protein |
| Comments/Corrections | |
Comment In:
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Cell Stem Cell. 2012 Mar 2;10(3):231-2
[PMID:
22385648
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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