Poster abstracts
Poster number 25 submitted by Chung-Ju Yeh
FGFR1 and FGFR4 are essential regulators of muscle stem cell quiescence
Chung-Ju Yeh (MCDB), Zipora Yablonka-Reuveni (Department of Neurobiology & Biophysics, University of Washington School of Medicine), Christoph Lepper (MCDB)
Abstract:
Satellite cells (SCs), the ‘bona fide’ stem cells of skeletal muscle, are maintained in a quiescent state during adult homeostasis. Yet, in response to severe injury, SCs readily activate, proliferate and differentiate along the myogenic lineage to provide myonuclei for new regenerative myofibers. A subset of SCs averts differentiation and re-enters into the quiescent stem cell state, hence, providing a self-renewing source of muscle reserve cells. A complex interplay of SC intrinsic and extrinsic molecular effectors is responsible for the finely tuned regulation of different SC activities. Among these effectors, several signaling pathways have been implicated in messaging physiological information to the SCs , including the FGF signaling pathway. However, the functions of the FGF receptors in adult SCs during homeostasis and injury-induced muscle regeneration are not fully understood. Here, we took an inducible conditional genetic approach to determine the combined contributions of the two predominantly expressed FGFRs in SCs, i.e. FGFR1 and FGFR4, to the molecular regulation of SCs. We discovered a surprising, unanticipated role of FGFR1/FGFR4 in SC quiescence maintenance during homeostasis by preventing their precocious differentiation. Moreover, we found that dual inactivation of both Fgfr1 and Fgfr4 results in impaired muscle regeneration and decreased SC self-renewal. In vitro assays revealed that Fgfr1/4 dually deficient SC-derived myoblasts are proliferation compromised and are more prone to terminally differentiate. Finally, we show that FGFR1/4 predominantly utilize the ERK signaling axis to promote SC proliferation and prevent their precocious differentiation. In conclusion, this study demonstrates a requirement for FGFR1/4 for SC quiescence maintenance and for balancing proliferation and differentiation of the SC lineage.
Keywords: satellite cell, muscle stem cell, FGF