Dystrophin Deficiency Leads to Genomic Instability in Human Pluripotent Stem Cells via NO Synthase-Induced Oxidative Stress
Abstract
:1. Introduction
2. Materials and Methods
2.1. Control Cell Lines and Cultivation
2.2. Tissue Processing, Reprogramming and Identification
2.3. CRISPR/Cas9 DMD hESC Clone Generation
2.4. Fluorescent Labeling
2.5. Inhibition Conditions
2.6. Mutation Frequency
2.7. Western Blot
2.8. Reverse Transcription PCR
2.9. Statistical Analysis
3. Results
3.1. Model DMD hPSC Cell Lines Harboring Dystrophin Mutation Are Pluripotent
3.2. WT hPSC, But Not DMD hPSC, Express High Molecular Weight Isoform of Dystrophin
3.3. Dystrophin Defect Leads to Elevated Oxidative Stress in DMD hPSC
3.4. Inhibition of NOS Activity Led to Decrease in ROS Production in DMD hPSC But Not in WT hPSC
3.5. NOS Activity Is Elevated in DMD hPSC Lines
3.6. Elevated ROS Leads to Elevated DNA Damage in DMD hPSC
3.7. NOS Activity Causes ROS Release Which Leads to DNA Damage in DMD hPSC
3.8. DNA Damage Increase in DMD hPSC Is Caused by nNOS, iNOS and eNOS Isoforms of NOS
3.9. Dystrophin Defect Leads to Compromised Genomic Stability of hPSC
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Jelinkova, S.; Fojtik, P.; Kohutova, A.; Vilotic, A.; Marková, L.; Pesl, M.; Jurakova, T.; Kruta, M.; Vrbsky, J.; Gaillyova, R.; et al. Dystrophin Deficiency Leads to Genomic Instability in Human Pluripotent Stem Cells via NO Synthase-Induced Oxidative Stress. Cells 2019, 8, 53. https://doi.org/10.3390/cells8010053
Jelinkova S, Fojtik P, Kohutova A, Vilotic A, Marková L, Pesl M, Jurakova T, Kruta M, Vrbsky J, Gaillyova R, et al. Dystrophin Deficiency Leads to Genomic Instability in Human Pluripotent Stem Cells via NO Synthase-Induced Oxidative Stress. Cells. 2019; 8(1):53. https://doi.org/10.3390/cells8010053
Chicago/Turabian StyleJelinkova, Sarka, Petr Fojtik, Aneta Kohutova, Aleksandra Vilotic, Lenka Marková, Martin Pesl, Tereza Jurakova, Miriama Kruta, Jan Vrbsky, Renata Gaillyova, and et al. 2019. "Dystrophin Deficiency Leads to Genomic Instability in Human Pluripotent Stem Cells via NO Synthase-Induced Oxidative Stress" Cells 8, no. 1: 53. https://doi.org/10.3390/cells8010053
APA StyleJelinkova, S., Fojtik, P., Kohutova, A., Vilotic, A., Marková, L., Pesl, M., Jurakova, T., Kruta, M., Vrbsky, J., Gaillyova, R., Valášková, I., Frák, I., Lacampagne, A., Forte, G., Dvorak, P., Meli, A. C., & Rotrekl, V. (2019). Dystrophin Deficiency Leads to Genomic Instability in Human Pluripotent Stem Cells via NO Synthase-Induced Oxidative Stress. Cells, 8(1), 53. https://doi.org/10.3390/cells8010053