Conditional TGF‐β1 treatment increases stem cell‐like cell population in myoblasts |
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| Authors: | Xiaodong Mu Yong Li |
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| Institution: | 1. The Laboratory of Molecular Pathology, Stem Cell Research Center (SCRC), Children’s Hospital of UPMC, Pittsburgh, PA, USA;2. Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA;3. Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA;4. Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA |
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| 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)‐β1. Our results show that a lower concentration of TGF‐β1 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‐β1 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‐β1 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‐β1 were also observed in the primary myoblasts of mice. Our results suggest that TGF‐β1 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. |
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| Keywords: | TGF‐β 1 dedifferentiation skeletal muscle stem cell multipotency |
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