Author contributions: S.G.B.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing; C.A.S.: data analysis and interpretation; C.M.K.: conception and design, financial support, data analysis and interpretation, and final approval of manuscript.
Original Research: Tissue-Specific Stem Cells
Article first published online: 14 FEB 2012
Copyright © 2011 AlphaMed Press
Volume 30, Issue 3, pages 548–560, March 2012
How to Cite
Ball, S. G., Shuttleworth, A. and Kielty, C. M. (2012), Inhibition of Platelet-Derived Growth Factor Receptor Signaling Regulates Oct4 and Nanog Expression, Cell Shape, and Mesenchymal Stem Cell Potency. STEM CELLS, 30: 548–560. doi: 10.1002/stem.1015
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS December 1, 2011.
- Issue published online: 14 FEB 2012
- Article first published online: 14 FEB 2012
- Accepted manuscript online: 28 DEC 2011 04:46PM EST
- Manuscript Accepted: 1 DEC 2011
- Manuscript Received: 17 MAY 2011
- Medical Research Council. Grant Number: G0700712
- Adult stem cells;
- Multipotential differentiation;
- Mesenchymal stem cells;
- Marrow stromal 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