Hypoxia-induced reprogrammed myoblasts enhance the formation of neuromuscular junctions: A pioneer study.

We previously reported that muscle cells could reprogram into progenitors after traumatic injuries. These injury-induced muscle stem cells (iMuSCs) have increased migration and differentiation capacities, including neuronal differentiation. Recent studies in our laboratory suggest that the hypoxia-induced by tissue injury plays an essential role in the reprogramming process of muscle cells. We hypothesize that muscle cells reprogrammed with hypoxia have increased neuronal differentiation potentials and the neuronal differentiation extends into the formation of neuromuscular junction (NMJ)-like structures. In this study, C2C12 myoblasts were cultured under hypoxic conditions and subsequently in neural differentiation media to generate neurospheres, and then with muscle differentiation media to induce NMJ-like structure formation. Hypoxia-induced muscle cells also produced more robust NMJs compared to controls after intramuscular cell transplantation. Our results suggest hypoxia plays a role in the reprogramming of muscle stem cells, which may have the potential to form neuromuscular junctions and ultimately contribute to functional muscle healing.