Numb-deficient satellite cells have regeneration and proliferation defects

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 myof...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2013-11, Vol.110 (46), p.18549-18554
Main Authors: George, Rajani M., Biressi, Stefano, Beres, Brian J., Rogers, Erik, Mulia, Amanda K., Allen, Ronald E., Rawls, Alan, Rando, Thomas A., Wilson-Rawls, Jeanne
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Artificial satellites
Barium Compounds
Biological Sciences
Blotting, Western
Body Weights and Measures
Cell culture
Cell growth
Cell Proliferation
Chlorides
Daughter cells
Flow Cytometry
Fluorescent Antibody Technique
Gene expression regulation
Membrane Proteins - deficiency
Mice
Mice, Knockout
Muscle Development - genetics
Muscle Development - physiology
Muscles
Muscular system
Myoblasts
Nerve Tissue Proteins - deficiency
Polymerase chain reaction
Progenitor cells
Proteins
Regeneration - genetics
Regeneration - physiology
Reverse Transcriptase Polymerase Chain Reaction
RNA Interference
RNA, Small Interfering - genetics
Satellite Cells, Skeletal Muscle - metabolism
Satellite Cells, Skeletal Muscle - physiology
Skeletal muscle
Skeletal muscle satellite cells
Stem cells
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1311628110