Cellular and molecular regulation of skeletal muscle side population cells.

Muscle progenitor cells (satellite cells) function in the maintenance and repair of adult skeletal muscle. Side population (SP) cells are enriched in repopulating activity and also reside in adult skeletal muscle. In this study, we observed that Abcg2 is a determinant of the SP cell phenotype. Using reverse transcription polymerase chain reaction and immunohistochemical techniques, we localized Abcg2-expressing cells in the interstitium and in close approximation to the vasculature of adult skeletal muscle. Muscle SP cells are able to differentiate into myotubes and increase in number after cardiotoxin-induced muscle injury. Similar to myogenic progenitor cells, muscle SP cells express Foxk1 and are decreased in number in Foxk1 mutant skeletal muscle. Using emerging technologies, we examine the molecular signature of muscle SP cells from normal, injured, and Foxk1 mutant skeletal muscle to define common and distinct molecular programs. We propose that muscle SP cells are progenitor cells that participate in repair and regeneration of adult skeletal muscle.