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.
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.
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
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.