Stem cells hold a great potential for the regeneration of damaged tissues in cardiovascular or musculoskeletal diseases. Unfortunately, problems such as limited availability, control of cell fate, and allograft rejection need to be addressed before therapeutic applications may become feasible. Generation of multipotent progenitors from adult differentiated cells could be a very attractive alternative to the limited in vitro self-renewal of several types of stem cells. In this direction, a recently synthesized unnatural purine, named reversine, has been proposed to induce reversion of adult cells to a multipotent state, which could be then converted into other cell types under appropriate stimuli. Our study suggests that reversine treatment transforms primary murine and human dermal fibroblasts into myogenic-competent cells both in vitro and in vivo. Moreover, this is the first study to demonstrate that plasticity changes arise in primary mouse and human cells following reversine exposure.