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Inhibition of Platelet-Derived Growth Factor Receptor Signaling Regulates Oct4 and Nanog Expression, Cell Shape, and Mesenchymal Stem Cell Potency
Defining the signaling mechanisms that regulate the fate of adult stem cells is an essential step toward their use in regenerative medicine. Platelet-derived growth factor receptor (PDGFR) signaling plays a crucial role in specifying mesenchymal stem cell (MSC) commitment to mesenchymal lineages. Ba...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wiley Subscription Services, Inc., A Wiley Company
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537888/ https://www.ncbi.nlm.nih.gov/pubmed/22213560 http://dx.doi.org/10.1002/stem.1015 |
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author | Ball, Stephen G Shuttleworth, Adrian Kielty, Cay M |
author_facet | Ball, Stephen G Shuttleworth, Adrian Kielty, Cay M |
author_sort | Ball, Stephen G |
collection | PubMed |
description | Defining the signaling mechanisms that regulate the fate of adult stem cells is an essential step toward their use in regenerative medicine. Platelet-derived growth factor receptor (PDGFR) signaling plays a crucial role in specifying mesenchymal stem cell (MSC) commitment to mesenchymal lineages. Based on the hypothesis that selective inhibition of signaling pathways involved in differentiation may increase stem cell potency, we examined the role of PDGFR signaling in controlling the fate of human MSCs. Using a small molecular PDGFR inhibitor that induced MSCs toward a more rounded shape, expression of Oct4 and Nanog were markedly upregulated. In these PDGFR inhibitor-treated MSCs, Oct4 and Nanog expression and cell shape were regulated by janus kinase (JAK), MAPK kinase (MEK), and epidermal growth factor receptor (EGFR) signaling. Under defined differentiation conditions, these PDGFR-inhibited MSCs expressed definitive endodermal, ectodermal, and mesodermal markers. We also confirmed that depletion of individual PDGF receptors upregulated expression of Oct4A and Nanog. This study identifies PDGFR signaling as a key regulator of Oct4 and Nanog expression and of MSC potency. Thus, inhibiting these specific receptor tyrosine kinases, which play essential roles in tissue formation, offers a novel approach to unlock the therapeutic capacity of MSCs. STEM CELLS 2012;30:548–560 |
format | Online Article Text |
id | pubmed-3537888 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Wiley Subscription Services, Inc., A Wiley Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-35378882013-01-09 Inhibition of Platelet-Derived Growth Factor Receptor Signaling Regulates Oct4 and Nanog Expression, Cell Shape, and Mesenchymal Stem Cell Potency Ball, Stephen G Shuttleworth, Adrian Kielty, Cay M Stem Cells Original Research: Tissue-Specific Stem Cells Defining the signaling mechanisms that regulate the fate of adult stem cells is an essential step toward their use in regenerative medicine. Platelet-derived growth factor receptor (PDGFR) signaling plays a crucial role in specifying mesenchymal stem cell (MSC) commitment to mesenchymal lineages. Based on the hypothesis that selective inhibition of signaling pathways involved in differentiation may increase stem cell potency, we examined the role of PDGFR signaling in controlling the fate of human MSCs. Using a small molecular PDGFR inhibitor that induced MSCs toward a more rounded shape, expression of Oct4 and Nanog were markedly upregulated. In these PDGFR inhibitor-treated MSCs, Oct4 and Nanog expression and cell shape were regulated by janus kinase (JAK), MAPK kinase (MEK), and epidermal growth factor receptor (EGFR) signaling. Under defined differentiation conditions, these PDGFR-inhibited MSCs expressed definitive endodermal, ectodermal, and mesodermal markers. We also confirmed that depletion of individual PDGF receptors upregulated expression of Oct4A and Nanog. This study identifies PDGFR signaling as a key regulator of Oct4 and Nanog expression and of MSC potency. Thus, inhibiting these specific receptor tyrosine kinases, which play essential roles in tissue formation, offers a novel approach to unlock the therapeutic capacity of MSCs. STEM CELLS 2012;30:548–560 Wiley Subscription Services, Inc., A Wiley Company 2012-03 2012-02-14 /pmc/articles/PMC3537888/ /pubmed/22213560 http://dx.doi.org/10.1002/stem.1015 Text en Copyright © 2011 AlphaMed Press http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. |
spellingShingle | Original Research: Tissue-Specific Stem Cells Ball, Stephen G Shuttleworth, Adrian Kielty, Cay M Inhibition of Platelet-Derived Growth Factor Receptor Signaling Regulates Oct4 and Nanog Expression, Cell Shape, and Mesenchymal Stem Cell Potency |
title | Inhibition of Platelet-Derived Growth Factor Receptor Signaling Regulates Oct4 and Nanog Expression, Cell Shape, and Mesenchymal Stem Cell Potency |
title_full | Inhibition of Platelet-Derived Growth Factor Receptor Signaling Regulates Oct4 and Nanog Expression, Cell Shape, and Mesenchymal Stem Cell Potency |
title_fullStr | Inhibition of Platelet-Derived Growth Factor Receptor Signaling Regulates Oct4 and Nanog Expression, Cell Shape, and Mesenchymal Stem Cell Potency |
title_full_unstemmed | Inhibition of Platelet-Derived Growth Factor Receptor Signaling Regulates Oct4 and Nanog Expression, Cell Shape, and Mesenchymal Stem Cell Potency |
title_short | Inhibition of Platelet-Derived Growth Factor Receptor Signaling Regulates Oct4 and Nanog Expression, Cell Shape, and Mesenchymal Stem Cell Potency |
title_sort | inhibition of platelet-derived growth factor receptor signaling regulates oct4 and nanog expression, cell shape, and mesenchymal stem cell potency |
topic | Original Research: Tissue-Specific Stem Cells |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537888/ https://www.ncbi.nlm.nih.gov/pubmed/22213560 http://dx.doi.org/10.1002/stem.1015 |
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