Efficient transdifferentiation of human dermal fibroblasts into skeletal muscle.

TitleEfficient transdifferentiation of human dermal fibroblasts into skeletal muscle.
Publication TypeJournal Article
Year of Publication2018
AuthorsSM Boularaoui, KMA Abdel-Raouf, NSA Alwahab, ME Kondash, GA Truskey, JCM Teo, and N Christoforou
JournalJournal of Tissue Engineering and Regenerative Medicine
Start Pagee918
Paginatione918 - e936
Date Published02/2018

Skeletal muscle holds significant regenerative potential but is incapable of restoring tissue loss caused by severe injury, congenital defects or tumour ablation. Consequently, skeletal muscle models are being developed to study human pathophysiology and regeneration. Their physiological accuracy, however, is hampered by the lack of an easily accessible human cell source that is readily expandable and capable of efficient differentiation. MYOD1, a master gene regulator, induces transdifferentiation of a variety of cell types into skeletal muscle, although inefficiently in human cells. Here we used MYOD1 to establish its capacity to induce skeletal muscle transdifferentiation of human dermal fibroblasts under baseline conditions. We found significant transdifferentiation improvement via transforming growth factor-β/activin signalling inhibition, canonical WNT signalling activation, receptor tyrosine kinase binding and collagen type I utilization. Mechanistically, manipulation of individual signalling pathways modulated the transdifferentiation process via myoblast proliferation, lowering the transdifferentiation threshold and inducing cell fusion. Overall, we used transdifferentiation to achieve the robust derivation of human skeletal myotubes and have described the signalling pathways and mechanisms regulating this process. Copyright © 2017 John Wiley & Sons, Ltd.

Short TitleJournal of Tissue Engineering and Regenerative Medicine