title: Myostatin acts as an autocrine/paracrine negative regulator in myoblast differentiation from human induced pluripotent stem cells.
abstract: Myostatin, also known as growth differentiation factor (GDF-8), regulates proliferation of muscle satellite cells, and suppresses differentiation of myoblasts into myotubes via down-regulation of key myogenic differentiation factors including MyoD. Recent advances in stem cell biology have enabled generation of myoblasts from pluripotent stem cells, but it remains to be clarified whether myostatin is also involved in regulation of artificial differentiation of myoblasts from pluripotent stem cells. Here we show that the human induced pluripotent stem (iPS) cell-derived cells that were induced to differentiate into myoblasts expressed myostatin and its receptor during the differentiation. An addition of recombinant human myostatin (rhMyostatin) suppressed induction of MyoD and Myo5a, resulting in significant suppression of myoblast differentiation. The rhMyostatin treatment also inhibited proliferation of the cells at a later phase of differentiation. RNAi-mediated silencing of myostatin promoted differentiation of human iPS-derived embryoid body (EB) cells into myoblasts. These results strongly suggest that myostatin plays an important role in regulation of myoblast differentiation from iPS cells of human origin. The present findings also have significant implications for potential regenerative medicine for muscular diseases.
authors.affiliation: Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Tsunao
authors.initials: T
authors.lastname: Kishida
authors.forename: Akika
authors.initials: A
authors.lastname: Ejima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Gojo
authors.forename: Osam
authors.initials: O
authors.lastname: Mazda
mesh_terms: D019898:Autocrine Communication; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D058732:Embryoid Bodies / Q000166:cytology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D017570:MyoD Protein / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D024701:Myosin Type V / Q000378:metabolism; D055435:Myostatin / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D019899:Paracrine Communication; D034622:RNA Interference
chemical_list: C525911:MSTN protein, human; D017570:MyoD Protein; D055435:Myostatin; C077511:MYO5A protein, human; D024701:Myosin Type V; D018995:Myosin Heavy Chains