JAK/STAT signaling and human in vitro myogenesis

Near confluent proliferating myoblasts were induced to differentiate for 1, 5 or 10 days. During these developmental stages, members of the JAK/STAT family were examined, along with factors known to regulate myogenesis. We demonstrate the phosphorylation of JAK1 and STAT1 only during myoblast proliferation, while JAK2 and STAT3 phosphorylation increases during differentiation. These increases were correlated with the upregulation of genes associated with muscle maturation and hypertrophy.Taken together, these results provide insight into JAK/STAT signaling in human skeletal muscle development, and confirm recent observations in rodents.Muscle fibres are terminally differentiated; therefore a population of quiescent satellite cells exists. These cells are thought to be responsible for postnatal muscle growth and injury-induced muscle regeneration [1]. Satellite cells are undifferentiated mononuclear cells, located within the basal lamina of the muscle fibre and reside in a dormant state until they are activated by physical activity or injury [2,3]. Upon activation they re-enter the cell cycle. Proliferating myoblasts expand their cytoplasmic-nuclei ratio and begin to fuse to existing fibres or with themselves to initiate de novo myofibre synthesis [3]. Muscle development is critically dependent on a family of myogenic regulatory factors (MRFs) including MyoD, Myf5, Myf6 and myogenin. They are temporally expressed to regulate the proliferation and differentiation of myoblasts, and often display overlapping roles. MyoD and Myf5 are expressed in actively proliferating cells prior to differentiation, while the expression of myogenin and Myf6 indicates that myoblasts have irreversibly withdrawn from the cell cycle and have commenced differentiation [4-7].Numerous intracellular signaling pathways and molecules have been found to play several roles in myogenic differentiation. These include MAPK and ERK, which elicit different signals to promote or inhibit differentiation a