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Tissue-Specific Stem Cells
Version of Record online: 24 MAR 2013
Copyright © 2013 AlphaMed Press
Volume 31, Issue 4, pages 823–828, April 2013
How to Cite
Lin, S., Shen, H., Jin, B., Gu, Y., Chen, Z., Cao, C., Hu, C., Keller, C., Pear, W. S. and Wu, L. (2013), Brief Report: Blockade of Notch Signaling in Muscle Stem Cells Causes Muscular Dystrophic Phenotype and Impaired Muscle Regeneration. STEM CELLS, 31: 823–828. doi: 10.1002/stem.1319
Author contributions: S.L.: collection of data, data analysis and interpretation, and manuscript writing; H.S., B.J., Y.G., Z.C., C.C. and C.H.: collection of data; C.K.: provision of study materials and manuscript writing; W.S.P.: provision of study materials; L.W.: conception and design, data analysis and interpretation, and manuscript writing.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS January 10, 2013.
- Issue online: 24 MAR 2013
- Version of Record online: 24 MAR 2013
- Manuscript Accepted: 27 NOV 2012
- Manuscript Revised: 23 NOV 2012
- Manuscript Received: 7 JUN 2012
- University of Florida Shands Cancer Center Startup
- Muscular Dystrophy Association
- Muscular dystrophy;
- Muscle stem cells;
Muscular dystrophies are a group of devastating diseases characterized by progressive muscle weakness and degeneration, with etiologies including muscle gene mutations and regenerative defects of muscle stem cells. Notch signaling is critical for skeletal myogenesis and has important roles in maintaining the muscle stem cell pool and preventing premature muscle differentiation. To investigate the functional impact of Notch signaling blockade in muscle stem cells, we developed a conditional knock-in mouse model in which endogenous Notch signaling is specifically blocked in muscle stem cell compartment. Mice with Notch signaling inhibition in muscle stem cells showed several muscular dystrophic features and impaired muscle regeneration. Analyses of satellite cells and isolated primary myoblasts revealed that Notch signaling blockade in muscle stem cells caused reduced activation and proliferation of satellite cells but enhanced differentiation of myoblasts. Our data thus indicate that Notch signaling controls processes that are critical to regeneration in muscular dystrophy, suggesting that Notch inhibitor therapies could have potential side effects on muscle functions. STEM CELLS 2013;31:823–828