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Efficient transdifferentiation of human dermal fibroblasts into skeletal muscle
Author(s) -
Boularaoui Selwa Mokhtar,
AbdelRaouf Khaled M.A.,
Alwahab Noaf Salah Ali,
Kondash Megan E.,
Truskey George A.,
Teo Jeremy Choon Meng,
Christoforou Nicolas
Publication year - 2018
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.2415
Subject(s) - transdifferentiation , myogenesis , skeletal muscle , microbiology and biotechnology , myocyte , biology , wnt signaling pathway , cellular differentiation , signal transduction , stem cell , endocrinology , genetics , gene
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.