BAMBI acts as a molecular switch to determine cell fate of C2C12 myoblasts

Myogenesis is a tightly regulated process by a cascade of well-coordinated events and pathways. Other than the known myogenic regulator factor (MRF) family including Myf5, MyoD, Myogenin and MRF4, our previous study identified BAMBI is involved in muscle regeneration and siRNA-mediated BAMBI knockdown impairs C2C12 myoblast differentiation. However, the potential role of BAMBI in determining cell linage and fate specification in C2C12 myoblast remains unexplored. In this study, we analyzed the RNA-seq data and discovered that BAMBI expression was dynamically regulated during proliferation and differentiation period of C2C12 myoblasts. By establishing cell line with the loss of function and gain of function of BAMBI in C2C12 myoblasts, we demonstrated that BAMBI deletion totally abrogated myogenic differentiation of C2C12 myoblast cells. In addition, loss of BAMBI converts C2C12 myoblasts to brown adipocytes through downregulation MyoD and upregulation of Prdm16. Conversely, BAMBI overexpression strikingly enhanced myogenic differentiation of C2C12 myoblasts by upregulating MyoD expression. Taken together, our results establish that BAMBI is a vital myogenic factor involved in myoblasts differentiation and as a key regulator governing the balance between myogenic and adipogenic lineage in C2C12 myoblast cells.