title: Human and mouse skeletal muscle stem cells: convergent and divergent mechanisms of myogenesis.
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.
authors.affiliation: Department of Medicine, Duke University, Durham, North Carolina, United States of America ; Muscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America.
authors.forename: Akshay
authors.initials: A
authors.lastname: Bareja
authors.affiliation: Muscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Holt
authors.affiliation: Muscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America.
authors.forename: Guizhen
authors.initials: G
authors.lastname: Luo
authors.affiliation: Five Prime Therapeutics, Inc., South San Francisco, California, United States of America.
authors.forename: Calvin
authors.initials: C
authors.lastname: Chang
authors.affiliation: Five Prime Therapeutics, Inc., South San Francisco, California, United States of America.
authors.forename: Junyu
authors.initials: J
authors.lastname: Lin
authors.affiliation: Five Prime Therapeutics, Inc., South San Francisco, California, United States of America.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Hinken
authors.affiliation: Quantitative Sciences, Computational Biology, GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Freudenberg
authors.affiliation: Department of Medicine, Duke University, Durham, North Carolina, United States of America.
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.affiliation: Muscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America.
authors.forename: William J
authors.initials: WJ
authors.lastname: Evans
authors.affiliation: Muscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Billin
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D015415:Biomarkers; C497417:MYF5 protein, human; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D051787:Myogenic Regulatory Factor 5; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human