Recent data on Duchenne muscular dystrophy (DMD) show myocyte progenitor's involvement in the disease pathology often leading to the DMD patient's death. The molecular mechanism underlying stem cell impairment in DMD has not been described. We created dystrophin-deficient human pluripotent stem cell (hPSC) lines by reprogramming cells from two DMD patients, and also by introducing dystrophin mutation into human embryonic stem cells via CRISPR/Cas9. While dystrophin is expressed in healthy hPSC, its deficiency in DMD hPSC lines induces the release of reactive oxygen species (ROS) through dysregulated activity of all three isoforms of nitric oxide synthase (further abrev. as, NOS). NOS-induced ROS release leads to DNA damage and genomic instability in DMD hPSC. We were able to reduce both the ROS release as well as DNA damage to the level of wild-type hPSC by inhibiting NOS activity.

• Klíčová slova
• DMD, NO synthases, ROS, dystrophin, genome stability, pluripotent stem cells,
• MeSH
• buněčné linie MeSH
• Duchennova muskulární dystrofie genetika   MeSH
• dystrofin nedostatek   genetika   MeSH
• indukované pluripotentní kmenové buňky metabolismus   patologie   MeSH
• lidé MeSH
• nestabilita genomu * MeSH
• oxidační stres MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• synthasa oxidu dusnatého, typ I metabolismus   MeSH
• synthasa oxidu dusnatého, typ II metabolismus   MeSH
• synthasa oxidu dusnatého, typ III metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dystrofin MeSH
• NOS1 protein, human MeSH Prohlížeč
• NOS2 protein, human MeSH Prohlížeč
• NOS3 protein, human MeSH Prohlížeč
• reaktivní formy kyslíku MeSH
• synthasa oxidu dusnatého, typ I MeSH
• synthasa oxidu dusnatého, typ II MeSH
• synthasa oxidu dusnatého, typ III MeSH