scholarly journals Precise Correction of the Dystrophin Gene in Duchenne Muscular Dystrophy Patient Induced Pluripotent Stem Cells by TALEN and CRISPR-Cas9

2015 ◽  
Vol 4 (1) ◽  
pp. 143-154 ◽  
Author(s):  
Hongmei Lisa Li ◽  
Naoko Fujimoto ◽  
Noriko Sasakawa ◽  
Saya Shirai ◽  
Tokiko Ohkame ◽  
...  
Keyword(s):  
Stem Cells ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Dystrophin Gene ◽  
Duchenne Muscular Dystrophy Patient ◽  
Induced Pluripotent

scholarly journals Orai1–STIM1 Regulates Increased Ca2+ Mobilization, Leading to Contractile Duchenne Muscular Dystrophy Phenotypes in Patient-Derived Induced Pluripotent Stem Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1589
Author(s):  
Tomoya Uchimura ◽  
Hidetoshi Sakurai
Keyword(s):  
Stem Cells ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Molecular Targets ◽  
Dystrophin Deficiency ◽  
Induced Pluripotent ◽  
Contractile Performance

Ca2+ overload is one of the factors leading to Duchenne muscular dystrophy (DMD) pathogenesis. However, the molecular targets of dystrophin deficiency-dependent Ca2+ overload and the correlation between Ca2+ overload and contractile DMD phenotypes in in vitro human models remain largely elusive. In this study, we utilized DMD patient-derived induced pluripotent stem cells (iPSCs) to differentiate myotubes using doxycycline-inducible MyoD overexpression, and searched for a target molecule that mediates dystrophin deficiency-dependent Ca2+ overload using commercially available chemicals and siRNAs. We found that several store-operated Ca2+ channel (SOC) inhibitors effectively prevented Ca2+ overload and identified that STIM1–Orai1 is a molecular target of SOCs. These findings were further confirmed by demonstrating that STIM1–Orai1 inhibitors, CM4620, AnCoA4, and GSK797A, prevented Ca2+ overload in dystrophic myotubes. Finally, we evaluated CM4620, AnCoA4, and GSK7975A activities using a previously reported model recapitulating a muscle fatigue-like decline in contractile performance in DMD. All three chemicals ameliorated the decline in contractile performance, indicating that modulating STIM1–Orai1-mediated Ca2+ overload is effective in rescuing contractile phenotypes. In conclusion, SOCs are major contributors to dystrophin deficiency-dependent Ca2+ overload through STIM1–Orai1 as molecular mediators. Modulating STIM1–Orai1 activity was effective in ameliorating the decline in contractile performance in DMD.

scholarly journals Early pathogenesis of Duchenne muscular dystrophy modelled in patient-derived human induced pluripotent stem cells

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Emi Shoji ◽  
Hidetoshi Sakurai ◽  
Tokiko Nishino ◽  
Tatsutoshi Nakahata ◽  
Toshio Heike ◽  
...  
Keyword(s):  
Stem Cells ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent

scholarly journals MODELING DUCHENNE MUSCULAR DYSTROPHY (DMD) CARDIOMYOPATHY USING HUMAN INDUCED PLURIPOTENT STEM CELLS (HIPSC)

2015 ◽  
Vol 65 (10) ◽  
pp. A2149
Author(s):  
Forum Kamdar ◽  
Andre Klaassen Kamdar ◽  
Christopher Chapman ◽  
Naoko Koyano Nakagawa ◽  
Daniel Garry
Keyword(s):  
Stem Cells ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent
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