Conversion of Committed Mouse Myoblasts into Muscle Stem Cells Using Small Molecules [RNA-Seq]

However, following prolonged propagation, myoblasts frequently lose myogenic differentiation capacity, limiting their utility in research and clinical applications. Here, we demonstrate that exposing committed mouse myoblasts to a small-molecule cocktail elicits their conversion into expandable and heterogeneous myogenic progenitor cells (MPCs), comprised of muscle stem, progenitor and differentiated cells.

Utilizing a new dual-fluorescent reporter for Pax7 and MyoD, we demonstrate that the small molecules de-differentiate Pax7+/MyoD+ myoblasts into Pax7+/MyoD- satellite-like cells within days. This conversion is characterized by upregulation of signaling pathways associated with satellite cells including Notch, Calcitonin and EGFR. Accordingly, genetic ablation of Notch1-expressing cells abrogated MPC cultures but not committed myoblasts.