Numb-deficient satellite cells have regeneration and proliferation defects

Rajani M. George, Stefano Biressi, Brian J. Beres, Erik Rogers, Amanda K. Mulia, Ronald E. Allen, Alan Rawls, Thomas A. Rando, Jeanne Wilson-Rawls

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)18549-18555
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number46
DOIs
StatePublished - Nov 12 2013

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Keywords

  • Conditional mutation
  • Myogenesis
  • Skeletal muscle
  • Stem cell

ASJC Scopus subject areas

  • General

Cite this

George, R. M., Biressi, S., Beres, B. J., Rogers, E., Mulia, A. K., Allen, R. E., Rawls, A., Rando, T. A., & Wilson-Rawls, J. (2013). Numb-deficient satellite cells have regeneration and proliferation defects. Proceedings of the National Academy of Sciences of the United States of America, 110(46), 18549-18555. https://doi.org/10.1073/pnas.1311628110