Efficient transdifferentiation of human dermal fibroblasts into skeletal muscle

Selwa Mokhtar Boularaoui, Khaled M.A. Abdel-Raouf, Noaf Salah Ali Alwahab, Megan E. Kondash, George A. Truskey, Jeremy Choon Meng Teo, Nicolas Christoforou

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)e918-e936
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume12
Issue number2
DOIs
StatePublished - Feb 1 2018

    Fingerprint

Keywords

  • TGFβ/activin
  • WNT
  • collagen type I
  • extracellular matrix
  • receptor tyrosine kinase
  • skeletal muscle
  • transdifferentiation

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering

Cite this

Boularaoui, S. M., Abdel-Raouf, K. M. A., Alwahab, N. S. A., Kondash, M. E., Truskey, G. A., Teo, J. C. M., & Christoforou, N. (2018). Efficient transdifferentiation of human dermal fibroblasts into skeletal muscle. Journal of Tissue Engineering and Regenerative Medicine, 12(2), e918-e936. https://doi.org/10.1002/term.2415