Skeletal muscle tissue possesses a tremendous capacity to regenerate after injury. Largely responsible for this formidable response is a small resident population of muscle stem cells. The current research efforts in the Lepper laboratory are geared towards determining the principle mechanisms regulating muscle stem cell expansion and entry into quiescence at a genome-wide level, as well as, single-gene functional level. In particular, we are investigating the molecular regulation underlying the acquisition of the correct number of muscle stem cells during the early postnatal period. This new line of research is leading us to focus on the role of the skeletal muscle fiber in the regulation of muscle stem cell pool size. To reach a deep and global understanding of this fundamental process, we are employing a combination of approaches including mouse genetics, molecular and cellular biology and ‘omic technologies.