Numb-deficient satellite cells have regeneration and proliferation defects

作者：George Rajani M; Biressi Stefano; Beres Brian J; Rogers Erik; Mulia Amanda K; Allen Ronald E; Rawls Alan; Rando Thomas A^*; Wilson Rawls Jeanne

来源：Proceedings of the National Academy of Sciences, 2013, 110(46): 18549-18554.

DOI：10.1073/pnas.1311628110

• myogenesis
• stem cell
• skeletal muscle
• conditional mutation

The adaptor protein Numb has been implicated in the switch between cell proliferation and differentiation made by satellite cells during muscle repair. Using two genetic approaches to ablate Numb, we determined that, in its absence, muscle regeneration in response to injury was impaired. Single myofiber cultures demonstrated a lack of satellite cell proliferation in the absence of Numb, and the proliferation defect was confirmed in satellite cell cultures. Quantitative RT-PCR from Numb-deficient satellite cells demonstrated highly up-regulated expression of p21 and Myostatin, both inhibitors of myoblast proliferation. Transfection with Myostatin-specific siRNA rescued the proliferation defect of Numb-deficient satellite cells. Furthermore, overexpression of Numb in satellite cells inhibited Myostatin expression. These data indicate a unique function for Numb during the initial activation and proliferation of satellite cells in response to muscle injury.

• 出版日期2013-11-12