The adult muscle satellite cells (MuSC) usually exist in a quiescent state in uninjured muscles and can be activated upon injury. It has been demonstrated in mouse models that a single intact myofiber or a single isolated MuSC could fully regenerate a piece of damaged muscle and replenish the quiescent MuSC pool after transplantation. Therefore, MuSC have great potentials in future clinical use to treat degenerative muscle diseases. One effective reagent to expand MuSC in culture is the fibroblast growth factor 2 (FGF2 or bFGF). Unexpectedly, we found that bFGF was able to elevate the expression of Pax7, a key MuSC-specific transcription factor indispensable for the maintenance of quiescent MuSC, at both mRNA and protein levels. The stimulatory effect of bFGF is partially media...[ Read more ]

The adult muscle satellite cells (MuSC) usually exist in a quiescent state in uninjured muscles and can be activated upon injury. It has been demonstrated in mouse models that a single intact myofiber or a single isolated MuSC could fully regenerate a piece of damaged muscle and replenish the quiescent MuSC pool after transplantation. Therefore, MuSC have great potentials in future clinical use to treat degenerative muscle diseases. One effective reagent to expand MuSC in culture is the fibroblast growth factor 2 (FGF2 or bFGF). Unexpectedly, we found that bFGF was able to elevate the expression of Pax7, a key MuSC-specific transcription factor indispensable for the maintenance of quiescent MuSC, at both mRNA and protein levels. The stimulatory effect of bFGF is partially mediated by the FGFR1-ERK signaling pathway. Moreover, the bFGF-treated MuSC were found to repair the damaged muscle and replenish the quiescent MuSC pool more efficiently than the PBS-treated MuSC. Our data suggest that bFGF regulates Pax7 expression through the FGFR1-ERK signaling pathway and maintains MuSC stemness during in vitro expansion.

Pax7 is important in both embryonic and neonatal muscle satellite cell development. Inducible deletion of Pax7 in adult muscle satellite cells in uninjured muscles leads to gradual depletion of the satellite cell pool and impairment in the proliferation of satellite cells in culture. However, it remains unclear how Pax7 exerts its functions in MuSC. By charactering the Pax7 knockout (Pax7-KO) mice, we found that gradual loss of MuSC pool in the absence of Pax7 likely results from cell apoptosis in vivo. More importantly, we demonstrated that Pax7 deletion in the quiescent MuSC decreased Myc level, which contributed to defective cell cycle re-entry. This cell cycle re-entry defect can be partially rescued by Myc overexpression. In our future studies, we will try to elucidate how Pax7 regulates Myc and apoptosis related genes by analyzing the RNA-seq, ATAC-seq, H3K27ac and H3K4me1 ChIP-seq data from both control and Pax7-KO mice. Hopefully, our works will unravel mechanistic details about the functions of Pax7 in adult MuSC.