Dissecting the Role of Myf6 in Facilitating Fibroblast Conversion into Myogenic Progenitor and Differentiated Cells [RNA-Seq]

Mechanistically, we characterized the chromatin binding of Myf6, as well as its protein binding partners, during iMPC reprogramming and conventional transdifferentiation, revealing shared and different targets and binding partners. To further investigate its role, we surprisingly found that endogenous Myf6 is dispensable for iMPC formation by MyoD and small molecules. In accordance with this observation, we demonstrated that subjecting MyoD-KO fibroblasts to reprogramming with Myf6 and small molecules gave rise to expandable MyoD-KO iMPCs, indicating that MyoD is similarly dispensable for iMPC formation and self-renewal.

Multi-omics analyses of Myf6-derived MyoD-KO iMPCs uncovered upregulated genes that compensated for the lack of MyoD, whose downregulation during iMPC production mitigated Pax7 expression, highlighting their roles as reprogramming regulators. Collectively, these results illustrate a redundancy between MRFs’ function in myogenic cellular conversions, highlighting an unexpected potency for Myf6 in the induction of a muscle stem cell fate in vitro.