Characterization of the role of CD34 in adult skeletal muscle regeneration

Expression of the cell surface sialomucin CD34 is common to many adult stem cell types, including muscle satellite cells. However, no clear stem cell or regeneration-related phenotype has ever been reported in mice lacking CD34, and its function on these cells remains poorly understood. Here, we assess the functional role of CD34 on satellite cell-mediated muscle regeneration. Using an optimized flow cytometry-based method to analyze myogenic progenitors, we show that CD34’s expression is tightly regulated early during the muscle regeneration process. Following this, we show that Cd34⁻/⁻ mice, which have no obvious developmental phenotype, display a defect in muscle regeneration when challenged with either acute or chronic muscle injury, resulting in impaired myofibre hypertrophy. In vivo engraftment efficiency and BrdU proliferation assays comparing WT and Cd34⁻/⁻ myogenic progenitors attribute this defect to impaired myogenic progenitor cell function in Cd34⁻/⁻ animals. Lastly, the culture of isolated single myofibres demonstrate that this overall muscle regenerative defect is caused by a delay in the activation of satellite cells lacking CD34 as well as impaired proliferation following activation. Consistent with the reported anti-adhesive function of CD34, Cd34⁻/⁻ satellite cells also show decreased motility along their host myofibre. Altogether, our results identify a role for CD34 in the poorly understood early steps of satellite cell activation, and provide the first evidence that beyond being a stem cell marker, CD34 may play an important function in modulating satellite cell activity.Medicine, Faculty ofMedicine, Department ofExperimental Medicine, Division ofGraduat