Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells
Abstract Satellite cells comprise a functionally heterogeneous population of stem cells in skeletal muscle. Separation of an undifferentiated subpopulation and elucidation of its molecular background are necessary to identify the reprogramming factors to induce skeletal muscle progenitor cells. In t...
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| Format: | Article |
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Nature Portfolio
2017-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-08232-2 |
| _version_ | 1818429562229358592 |
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| author | Naoki Ito Isao Kii Noriaki Shimizu Hirotoshi Tanaka Shin’ichi Takeda |
| author_facet | Naoki Ito Isao Kii Noriaki Shimizu Hirotoshi Tanaka Shin’ichi Takeda |
| author_sort | Naoki Ito |
| collection | DOAJ |
| description | Abstract Satellite cells comprise a functionally heterogeneous population of stem cells in skeletal muscle. Separation of an undifferentiated subpopulation and elucidation of its molecular background are necessary to identify the reprogramming factors to induce skeletal muscle progenitor cells. In this study, we found that intracellular esterase activity distinguishes a subpopulation of cultured satellite cells with high stemness using esterase-sensitive cell staining reagent, calcein-AM. Gene expression analysis of this subpopulation revealed that defined combinations of transcription factors (Pax3, Mef2b, and Pitx1 or Pax7, Mef2b, and Pitx1 in embryonic fibroblasts, and Pax7, Mef2b and MyoD in adult fibroblasts) reprogrammed fibroblasts into skeletal muscle progenitor cells. These reprogrammed cells formed Dystrophin-positive mature muscle fibers when transplanted into a mouse model of Duchenne muscular dystrophy. These results highlight the new marker for heterogenous population of cultured satellite cells, potential therapeutic approaches and cell sources for degenerative muscle diseases. |
| first_indexed | 2024-12-14T15:19:29Z |
| format | Article |
| id | doaj.art-2192f1b78b2b4c83b213bbecf54c7814 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T15:19:29Z |
| publishDate | 2017-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2192f1b78b2b4c83b213bbecf54c78142022-12-21T22:56:13ZengNature PortfolioScientific Reports2045-23222017-08-017111210.1038/s41598-017-08232-2Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cellsNaoki Ito0Isao Kii1Noriaki Shimizu2Hirotoshi Tanaka3Shin’ichi Takeda4Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and PsychiatryPathophysiological and Health Science Team, Imaging Application Group, Division of Bio-Function Dynamics Imaging, Riken Center for Life Science TechnologiesDivision of Rheumatology, Center for Antibody and Vaccine Therapy, IMSUT Hospital, The Institute of Medical Science, The University of TokyoDepartment of Rheumatology and Allergy, IMSUT Hospital, The Institute of Medical Science, The University of TokyoDepartment of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and PsychiatryAbstract Satellite cells comprise a functionally heterogeneous population of stem cells in skeletal muscle. Separation of an undifferentiated subpopulation and elucidation of its molecular background are necessary to identify the reprogramming factors to induce skeletal muscle progenitor cells. In this study, we found that intracellular esterase activity distinguishes a subpopulation of cultured satellite cells with high stemness using esterase-sensitive cell staining reagent, calcein-AM. Gene expression analysis of this subpopulation revealed that defined combinations of transcription factors (Pax3, Mef2b, and Pitx1 or Pax7, Mef2b, and Pitx1 in embryonic fibroblasts, and Pax7, Mef2b and MyoD in adult fibroblasts) reprogrammed fibroblasts into skeletal muscle progenitor cells. These reprogrammed cells formed Dystrophin-positive mature muscle fibers when transplanted into a mouse model of Duchenne muscular dystrophy. These results highlight the new marker for heterogenous population of cultured satellite cells, potential therapeutic approaches and cell sources for degenerative muscle diseases.https://doi.org/10.1038/s41598-017-08232-2 |
| spellingShingle | Naoki Ito Isao Kii Noriaki Shimizu Hirotoshi Tanaka Shin’ichi Takeda Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells Scientific Reports |
| title | Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells |
| title_full | Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells |
| title_fullStr | Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells |
| title_full_unstemmed | Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells |
| title_short | Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells |
| title_sort | direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells |
| url | https://doi.org/10.1038/s41598-017-08232-2 |
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