Characterization of RBL2 in Muscle Stem Cell Fate Decisions

Skeletal muscle stem cells (MuSCs) regenerate muscle upon injury. Here, they receive activation signals from their environment and make a fate decision to make further copies (self-renew) or commit to becoming muscle (differentiate). Dysfunctional MuSC fate decisions, lead to poor muscle quality. Accordingly, retinoblastoma-like protein 2 (Rbl2) was characterized in MuSC fate decisions. Targeted deletion of Rbl2 in muscle progenitors impaired myotube formation, demonstrating its potential requirement for MuSC function. Rbl2 was analyzed during MuSC fate decisions by immunostaining cultured myofibers with Pax7 and MyoD. Rbl2 was expressed in the nucleus of only a fraction of committed MuSCs. Surprisingly, during a differentiation time course, primary myogenic progenitor cells expressed Rbl2 in the mitochondria. The Rbl2 expression in the mitochondria of differentiating MuSCs was confirmed in vivo by immunohistochemistry. These results provide novel insights for the localization of Rbl2 in MuSC fate decisions and the mechanisms driving differentiation.