Abstract
Satellite cells are the chief contributor to skeletal muscle growth and regeneration. The study of mouse satellite cells has accelerated in recent years due to technical advancements in the isolation of these cells. The study of human satellite cells has lagged and thus little is known about how the biology of mouse and human satellite cells compare. We developed a flow cytometry-based method to prospectively isolate human skeletal muscle progenitors from the satellite cell pool using positive and negative selection markers. Results show that this pool is enriched in PAX7 expressing cells that possess robust myogenic potential including the ability to give rise to de novo muscle in vivo. We compared mouse and human satellite cells in culture and identify differences in the elaboration of the myogenic genetic program and in the sensitivity of the cells to cytokine stimulation. These results indicate that not all mechanisms regulating mouse satellite cell activation are conserved in human satellite cells and that such differences may impact the clinical translation of therapeutics validated in mouse models. Thus, the findings of this study are relevant to developing therapies to combat muscle disease.
Highlights
Satellite cells are rare, mononuclear cells located adjacent to skeletal muscle, in between the sarcolemma and the basal lamina of the surrounding extracellular matrix [1]
fluorescence-activated cell sorting (FACS) Isolation of Human Skeletal Muscle Precursors Previous studies have identified the CD342/CD56+ population of myogenic cells derived from human skeletal muscle [10]
Research on human satellite cells has lagged behind, and only a fraction of the reported studies have made use of FACS to isolate the cells. The majority of such studies employ methods that include extended periods of culturing [25,26,27,28], and it has been firmly established that satellite cells rapidly lose quiescence to become committed myogenic cells soon after being exposed to cell culture conditions [7]
Summary
Mononuclear cells located adjacent to skeletal muscle, in between the sarcolemma and the basal lamina of the surrounding extracellular matrix [1] They are mitotically quiescent under normal conditions, and become activated in response to external stimuli like exercise or injury. Flow cytometry-based techniques have been developed to prospectively isolate pure populations of satellite cells from their niche. These cells have been unambiguously shown to display myogenic stem cell properties, such as the ability to self-renew and give rise to differentiated muscle cells both in vitro and in vivo [4,5,6]. These drawbacks include the inability to produce a pure population of cells and, due to the length of these procedures, the isolated cells are more likely to be committed progenitor cells as opposed to genuine satellite cell derived precursors ([7]; for detailed discussion, refer to [8])
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