Two microRNAs enable adult muscle stem cells to reach their full potential, Chen et al. reveal. The regulatory molecules block a transcription factor that curtails the cells' differentiation.
Most of the time, muscle stem cells, or satellite cells, do little except slowly divide. After an injury, however, they activate and help build new muscle fibers. The transcription factor Pax7 is necessary for stem cell maintenance under normal conditions. Once the cells are activated, Pax7 switches on the genes necessary for early differentiation. But Pax7 also stops the cells from terminally differentiating, so Pax7 must be shut down to allow the differentiation program to proceed. To find out how, Chen et al. focused on microRNAs, which they had previously shown were crucial during embryonic muscle development.
By tracking the differentiation of cultured satellite cells, the researchers identified two microRNAs—miR-1 and miR-206—that were necessary for the process. The team found that boosting the amounts of miR-1 and miR-206 in satellite cells slowed their division and sped up their specialization. Both microRNAs reduced Pax7 levels but, because an individual microRNA can quell multiple target genes, Chen et al. speculate that miR-1 and miR-206 shut down other genes involved in stem cell maintenance.