Molecular regulation of muscle stem cells by 'quiescence genes'

Skeletal muscle has great regenerative potential that depends on muscle stem cells, called satellite cells. In uninjured muscle, satellite cells reside beneath the basal lamina and are maintained in quiescent and undifferentiated state. This state is considered a requisite for sustaining the satellite cell pool, but the molecular mechanism is still unknown. In our previous study, we developed a novel monoclonal antibody that specifically recognized muscle satellite cells in skeletal muscle. Using this monoclonal antibody, we purified satellite cells and performed genome-wide transcriptome analysis. In these analyses, we found that satellite cells expressed Hesr1/Hey1 and Hesr3/HeyL genes known as down stream target of Notch signaling. Although each single knock out mice did not indicate obvious phenotype in skeletal muscle, Hesr1/Hesr3 double knock out mice showed remarkably decreased number of satellite cells. Intriguingly, dKO satellite cells were not kept in quiescent and differentiated state in adult skeletal muscle. This dysregulated state of satellite cells lead to gradually decreased number of satellite cells and age-dependent regeneration defect. These results indicate that Hesr1/3 is essential for muscle stem cell biology and will facilitate this research field.