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Tissue-Specific Stem Cells
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The Egf Receptor-Sox2-Egf Receptor Feedback Loop Positively Regulates the Self-Renewal of Neural Precursor Cells†‡§
Article first published online: 30 OCT 2009
DOI: 10.1002/stem.246
Copyright © 2010 AlphaMed Press
Additional Information
How to Cite
Hu, Q., Zhang, L., Wen, J., Wang, S., Li, M., Feng, R., Yang, X. and Li, L. (2010), The Egf Receptor-Sox2-Egf Receptor Feedback Loop Positively Regulates the Self-Renewal of Neural Precursor Cells. STEM CELLS, 28: 279–286. doi: 10.1002/stem.246
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Author contributions: Q.H.: provision of study materials, experiment performance; L.Z.: experiment performance, collection and assembly of data; J.W.: experiment design and performance, data analysis, approval of manuscript; Q.H., L.Z., and J.W.: contributed equally to this work; S.W.: tissue sections, immunofluorescence staining; M.L.: cell culture, PCR analysis; R.F.: provision of study materials, neural cell culture; X.Y.: technique assistance, provision of study materials; L.L.: conception and design, financial support, manuscript writing, final approval of manuscript.
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First published online in STEM CELLSEXPRESS January 28, 2010.
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Disclosure of potential conflicts of interest is found at the end of this article.
Publication History
- Issue published online: 16 FEB 2010
- Article first published online: 30 OCT 2009
- Accepted manuscript online: 30 OCT 2009 12:00AM EST
- Manuscript Accepted: 22 OCT 2009
- Manuscript Received: 9 JUN 2009
Funded by
- Chinese National 863 Projects. Grant Number: 2006AA02A114
- Beijing Ministry of Science and Technology. Grant Number: D07050701350704
- Chinese National 973 Projects. Grant Number: 2006CB943603
- Peking University Stem Cell Center. Grant Number: 2006CB503905
- Ministry of Science and Technology for International Collaboration Project. Grant Number: 2007DFC31650863
- National Natural Science Foundation of China. Grant Numbers: Project 30871251, Project 30960150
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Keywords:
- Neural procursor cells;
- Egfr;
- Sox2;
- Self-renewal
Abstract
The transcriptional factor Sox2 and epidermal growth factor receptor (Egfr)-mediated signaling are both required for self-renewal of neural precursor cells (NPCs). However, the mechanism by which these factors coordinately regulate this process is largely unknown. Here we show that Egfr-mediated signaling promotes Sox2 expression, which in turn binds to the Egfr promoter and directly upregulates Egfr expression. Knockdown of Sox2 by RNA interference downregulates Egfr expression and attenuates colony formation of NPCs, whereas overexpression of Sox2 elevates Egfr expression and promotes NPC self-renewal. Moreover, the effect of Sox2 on NPC self-renewal is completely inhibited by AG1478, a specific inhibitor for Egfr; it is also inhibited by LY294002 and U0126, selective antagonists for phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase (Erk1/2), respectively. Collectively, we conclude that NPC self-renewal is enhanced through a novel cellular feedback loop with mutual regulation of Egfr and Sox2. STEM CELLS 2010;28:279–286