Back
Efficient transdifferentiation of human dermal fibroblasts into skeletal muscle.
Journal article

Efficient transdifferentiation of human dermal fibroblasts into skeletal muscle.

  • Boularaoui SM Department of Biomedical Engineering, Khalifa University, Abu Dhabi, UAE.
  • Abdel-Raouf KMA Department of Biomedical Engineering, Khalifa University, Abu Dhabi, UAE.
  • Alwahab NSA School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Kondash ME Department of Biomedical Engineering, Duke University, Durham, NC, USA.
  • Truskey GA Department of Biomedical Engineering, Duke University, Durham, NC, USA.
  • Teo JCM Department of Biomedical Engineering, Khalifa University, Abu Dhabi, UAE.
  • Christoforou N Department of Biomedical Engineering, Khalifa University, Abu Dhabi, UAE.
Show more…
  • 2017-01-20
Published in:
  • Journal of tissue engineering and regenerative medicine. - 2018
TGFβ/activin
WNT
collagen type I
extracellular matrix
receptor tyrosine kinase
skeletal muscle
transdifferentiation
Animals
Calcium
Cell Fusion
Cell Line
Cell Transdifferentiation
Cytoskeleton
Dermis
Extracellular Matrix
Fibroblasts
HEK293 Cells
Humans
Mice
Muscle, Skeletal
MyoD Protein
Optical Imaging
Phenotype
Signal Transduction
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/180548
Statistics
Document views: 36 File downloads: