Inhibition of the Combinatorial Signaling of Transforming Growth Factor-Beta and NOTCH Promotes Myotube Formation of Human Pluripotent Stem Cell-Derived Skeletal Muscle Progenitor Cells.
In Young ChoiHo Tae LimYoung Hyun CheGabsang LeeYong Jun KimPublished in: Cells (2021)
Understanding the signaling pathways that regulate the final differentiation of human myoblasts is essential for successful cell transplantation and drug screening for the treatment of muscular dystrophy. In an effort to improve myotube formation from hiPSC-derived myoblasts, we validated a collection of 13 small molecules in a newly established in vitro screening platform for the assessment of myotube formation. The analysis of myotube formation as measured by the fusion index showed that the combinational inhibition of the TGFβ signaling with NOTCH signaling enhances the ability of multi-nucleated myotube production. Combinational treatment of inhibitors for TGFβ and NOTCH signaling pathways improved myotube formation in a dose-dependent manner. This effect was achieved by inhibiting the combinatorial mechanism of signaling. The combination treatment of small molecules effective in inducing multinucleated myotubes was validated in healthy human primary myoblasts. In addition, it was also applied to DMD patient iPSC-derived myoblasts to enhance the generation of multinucleated myotubes.
Keyphrases
- transforming growth factor
- endothelial cells
- signaling pathway
- skeletal muscle
- epithelial mesenchymal transition
- induced pluripotent stem cells
- muscular dystrophy
- cell proliferation
- type diabetes
- emergency department
- cell therapy
- duchenne muscular dystrophy
- pluripotent stem cells
- stem cells
- oxidative stress
- high throughput
- insulin resistance
- case report
- pi k akt