Chemical reprogramming of melanocytes to skeletal muscle cells
Abstract Background Direct cell‐fate conversion by chemical reprogramming is promising for regenerative cell therapies. However, this process requires the reactivation of a set of master transcription factors (TFs) of the target cell type, which has proven challenging using only small molecules. Met...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-04-01
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| Series: | Journal of Cachexia, Sarcopenia and Muscle |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jcsm.13155 |
| _version_ | 1797854125556236288 |
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| author | Wenjun Yang Yaqi Wang Yuanyuan Du Jiyong Li Minzhi Jia Sheng Li Ruimiao Ma Cheng Li Hongkui Deng Ping Hu |
| author_facet | Wenjun Yang Yaqi Wang Yuanyuan Du Jiyong Li Minzhi Jia Sheng Li Ruimiao Ma Cheng Li Hongkui Deng Ping Hu |
| author_sort | Wenjun Yang |
| collection | DOAJ |
| description | Abstract Background Direct cell‐fate conversion by chemical reprogramming is promising for regenerative cell therapies. However, this process requires the reactivation of a set of master transcription factors (TFs) of the target cell type, which has proven challenging using only small molecules. Methods We developed a novel small‐molecule cocktail permitting robust skin cell to muscle cell conversion. By single cell sequencing analysis, we identified a Pax3 (Paired box 3)‐expressing melanocyte population holding a superior myogenic potential outperforming other seven types of skin cells. We further validated the single cell sequencing analysis results using immunofluorescence staining, in situ hybridization and FACS sorting and confirmed the myogenic potential of melanocytes during chemical reprogramming. We used single cell RNA‐seq that detect the potential converted cell type, uncovering a unique role of Pax3 in facilitating chemical reprogramming from melanocytes to muscle cells. Results In this study, we demonstrated that the Pax3‐expressing melanocytes to be a skin cell type for skeletal muscle cell fate conversion in chemical reprogramming. By developing a small‐molecule cocktail, we showed an efficient melanocyte reprogramming to skeletal muscle cells (40%, P < 0.001). The endogenous expression of specific TFs may circumvent the additional requirement for TF reactivation and form a shortcut for cell fate conversion, suggesting a basic principle that could ease cell fate conversion. Conclusions Our study demonstrates the first report of melanocyte‐to‐muscle conversion by small molecules, suggesting a novel strategy for muscle regeneration. Furthermore, skin is one of the tissues closely located to skeletal muscle, and therefore, our results provide a promising foundation for therapeutic chemical reprogramming in vivo treating skeletal muscle degenerative diseases. |
| first_indexed | 2024-04-09T20:01:55Z |
| format | Article |
| id | doaj.art-55dffe771c5f4af7ab6938a6ea68854d |
| institution | Directory Open Access Journal |
| issn | 2190-5991 2190-6009 |
| language | English |
| last_indexed | 2024-04-09T20:01:55Z |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Cachexia, Sarcopenia and Muscle |
| spelling | doaj.art-55dffe771c5f4af7ab6938a6ea68854d2023-04-03T02:38:50ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092023-04-0114290391410.1002/jcsm.13155Chemical reprogramming of melanocytes to skeletal muscle cellsWenjun Yang0Yaqi Wang1Yuanyuan Du2Jiyong Li3Minzhi Jia4Sheng Li5Ruimiao Ma6Cheng Li7Hongkui Deng8Ping Hu9Department of Pediatric Orthopedics Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Guangzhou Laboratory‐Guangzhou Medical University, Guangzhou, China; School of life Sciences, Center for Bioinformatics, Center for Statistical Science, Peking University Beijing ChinaDepartment of Pediatric Orthopedics Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Guangzhou Laboratory‐Guangzhou Medical University, Guangzhou, China; School of life Sciences, Center for Bioinformatics, Center for Statistical Science, Peking University Beijing ChinaMOE Engineering Research Center of Regenerative Medicine, School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking‐Tsinghua Center for LifeSciences Peking University Beijing ChinaState Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science Chinese Academy of Sciences Shanghai ChinaState Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science Chinese Academy of Sciences Shanghai ChinaDepartment of Pediatric Orthopedics Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Guangzhou Laboratory‐Guangzhou Medical University, Guangzhou, China; School of life Sciences, Center for Bioinformatics, Center for Statistical Science, Peking University Beijing ChinaDepartment of Pediatric Orthopedics Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Guangzhou Laboratory‐Guangzhou Medical University, Guangzhou, China; School of life Sciences, Center for Bioinformatics, Center for Statistical Science, Peking University Beijing ChinaDepartment of Pediatric Orthopedics Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Guangzhou Laboratory‐Guangzhou Medical University, Guangzhou, China; School of life Sciences, Center for Bioinformatics, Center for Statistical Science, Peking University Beijing ChinaMOE Engineering Research Center of Regenerative Medicine, School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking‐Tsinghua Center for LifeSciences Peking University Beijing ChinaDepartment of Pediatric Orthopedics Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Guangzhou Laboratory‐Guangzhou Medical University, Guangzhou, China; School of life Sciences, Center for Bioinformatics, Center for Statistical Science, Peking University Beijing ChinaAbstract Background Direct cell‐fate conversion by chemical reprogramming is promising for regenerative cell therapies. However, this process requires the reactivation of a set of master transcription factors (TFs) of the target cell type, which has proven challenging using only small molecules. Methods We developed a novel small‐molecule cocktail permitting robust skin cell to muscle cell conversion. By single cell sequencing analysis, we identified a Pax3 (Paired box 3)‐expressing melanocyte population holding a superior myogenic potential outperforming other seven types of skin cells. We further validated the single cell sequencing analysis results using immunofluorescence staining, in situ hybridization and FACS sorting and confirmed the myogenic potential of melanocytes during chemical reprogramming. We used single cell RNA‐seq that detect the potential converted cell type, uncovering a unique role of Pax3 in facilitating chemical reprogramming from melanocytes to muscle cells. Results In this study, we demonstrated that the Pax3‐expressing melanocytes to be a skin cell type for skeletal muscle cell fate conversion in chemical reprogramming. By developing a small‐molecule cocktail, we showed an efficient melanocyte reprogramming to skeletal muscle cells (40%, P < 0.001). The endogenous expression of specific TFs may circumvent the additional requirement for TF reactivation and form a shortcut for cell fate conversion, suggesting a basic principle that could ease cell fate conversion. Conclusions Our study demonstrates the first report of melanocyte‐to‐muscle conversion by small molecules, suggesting a novel strategy for muscle regeneration. Furthermore, skin is one of the tissues closely located to skeletal muscle, and therefore, our results provide a promising foundation for therapeutic chemical reprogramming in vivo treating skeletal muscle degenerative diseases.https://doi.org/10.1002/jcsm.13155MelanocytesSkeletal muscle cellsReprogrammingSmall molecules |
| spellingShingle | Wenjun Yang Yaqi Wang Yuanyuan Du Jiyong Li Minzhi Jia Sheng Li Ruimiao Ma Cheng Li Hongkui Deng Ping Hu Chemical reprogramming of melanocytes to skeletal muscle cells Journal of Cachexia, Sarcopenia and Muscle Melanocytes Skeletal muscle cells Reprogramming Small molecules |
| title | Chemical reprogramming of melanocytes to skeletal muscle cells |
| title_full | Chemical reprogramming of melanocytes to skeletal muscle cells |
| title_fullStr | Chemical reprogramming of melanocytes to skeletal muscle cells |
| title_full_unstemmed | Chemical reprogramming of melanocytes to skeletal muscle cells |
| title_short | Chemical reprogramming of melanocytes to skeletal muscle cells |
| title_sort | chemical reprogramming of melanocytes to skeletal muscle cells |
| topic | Melanocytes Skeletal muscle cells Reprogramming Small molecules |
| url | https://doi.org/10.1002/jcsm.13155 |
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