Authors:
A Sacco, R Doyonnas, P Kraft, & H M Blau
Summary:
Adult muscle stem cells (MuSCs) play a major role in postnatal skeletal muscle growth and regeneration. Yet, much remains to be learned about the cell biological properties of MuSCs. These stem cells comprise a subset of satellite cells, that reside as quiescent cells underneath
the basal lamina that surrounds muscle fibers and respond to damage by giving rise to transient amplifying cells (progenitors) and myoblasts that fuse with myofibers. In contrast to cultured myoblasts, when freshly isolated by flow cytometry and immediately transplanted into
muscle tissues, MuSCs exhibit remarkable regenerative capacity. However, since MuSCs are known to be heterogeneous, a clonal analysis is required to demonstrate stem cell function. We have shown that when a single luciferase-expressing MuSC is transplanted into the muscle of
mice, it is capable of extensive proliferation, and Pax7+luciferase+ cells can be readily reisolated, providing definitive evidence of selfrenewal. In addition, we show using in vivo bioluminescence imaging, that the dynamics of MuSC behavior can be followed in a manner not
possible using traditional retrospective static histological analyses. By imaging luciferase activity, real time quantitative and kinetic analyses show that MuSCs proliferate and engraft rapidly following injection until homeostasis is reached. Upon injury, transplanted mononucleated cells rapidly generate massive waves of cell proliferation. Together, these results show the dynamics of MuSC behavior and provide novel evidence at a clonal level that self-renewal is an autonomous property of a single adult muscle stem cell.
Source:
American Society for Cell Biology (ASCB) 48th Annual Meeting; San Francisco, CA, Dec. 13-17, 628/B590, Page 182 (12/14/08)