title: Conditional TGF-β1 treatment increases stem cell-like cell population in myoblasts.
abstract: The limitation in successfully acquiring large populations of stem cell has impeded their application. A new method based on the dedifferentiation of adult somatic cells to generate induced multipotent stem cells would allow us to obtain a large amount of autologous stem cells for regenerative medicine. The current work was proposed to induce a sub-population of cells with characteristics of muscle stem cells from myoblasts through conditional treatment of transforming growth factor (TGF)-β(1) . Our results show that a lower concentration of TGF-β(1) is able to promote C2C12 myoblasts to express stem cell markers as well as to repress myogenic proteins, which involves a mechanism of dedifferentiation. Moreover, TGF-β(1) treatment promoted the proliferation-arrested C2C12 myoblasts to re-enter the S-phase. We also investigated the multi-differentiation potentials of the dedifferentiated cells. TGF-β(1) pre-treated C2C12 myoblasts were implanted into mice to repair dystrophic skeletal muscle or injured bone. In addition to the C2C12 myoblasts, similar effects of TGF-β(1) were also observed in the primary myoblasts of mice. Our results suggest that TGF-β(1) is effective as a molecular trigger for the dedifferentiation of skeletal muscle myoblasts and could be used to generate a large pool of progenitor cells that collectively behave as multipotent stem cell-like cells for regenerative medicine applications.
authors.affiliation: The Laboratory of Molecular Pathology, Stem Cell Research Center, Children's Hospital of UPMC, Pittsburgh, PA, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Mu
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D054337:Cell Dedifferentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology / Q000601:surgery; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D053773:Transforming Growth Factor beta1