دورية أكاديمية
c-Myc Inhibitor 10074-G5 Induces Murine and Human Hematopoietic Stem and Progenitor Cell Expansion and HDR Modulator Rad51 Expression
| العنوان: | c-Myc Inhibitor 10074-G5 Induces Murine and Human Hematopoietic Stem and Progenitor Cell Expansion and HDR Modulator Rad51 Expression |
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| المؤلفون: | Aksoz, Merve, Albayrak, Esra, Aslan, Galip Servet, Turan, Raife Dilek, Alyazici, Lamia Yazgi, Siyah, Pınar, Tuysuz, Emre Can, Canikyan, Serli, Yucel, Dogacan, Meric, Neslihan, Gulbas, Zafer, Sahin, Fikrettin, Kocabas, Fatih |
| المساهمون: | International Centre for Genetic Engineering and Biotechnology, ICGEB, Science Academy Young Scientist Award Program, Scientific and Technological Research Council of Turkey |
| المصدر: | Current Cancer Drug Targets ; volume 19, issue 6, page 479-494 ; ISSN 1568-0096 |
| بيانات النشر: | Bentham Science Publishers Ltd. |
| سنة النشر: | 2019 |
| الوصف: | Background: c-Myc plays a major role in the maintenance of glycolytic metabolism and hematopoietic stem cell (HSC) quiescence. Objective: Targeting modulators of HSC quiescence and metabolism could lead to HSC cell cycle entry with concomitant expansion. Methods and Results: Here we show that c-Myc inhibitor 10074-G5 treatment leads to 2-fold increase in murine LSKCD34low HSC compartment post 7 days. In addition, c-Myc inhibition increases CD34+ and CD133+ human HSC number. c-Myc inhibition leads to downregulation of glycolytic and cyclindependent kinase inhibitor (CDKI) gene expression ex vivo and in vivo. In addition, c-Myc inhibition upregulates major HDR modulator Rad51 expression in hematopoietic cells. Besides, c-Myc inhibition does not alter proliferation kinetics of endothelial cells, fibroblasts or adipose-derived mesenchymal stem cells, however, it limits bone marrow derived mesenchymal stem cell proliferation. We further demonstrate that a cocktail of c-Myc inhibitor 10074-G5 along with tauroursodeoxycholic acid (TUDCA) and i-NOS inhibitor L-NIL provides a robust HSC maintenance and expansion ex vivo as evident by induction of all stem cell antigens analyzed. Intriguingly, the cocktail of c-Myc inhibitor 10074-G5, TUDCA and L-NIL improves HDR related gene expression. Conclusion: These findings provide tools to improve ex vivo HSC maintenance and expansion, autologous HSC transplantation and gene editing through modulation of HSC glycolytic and HDR pathways. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.2174/1568009618666180905100608 |
| الإتاحة: | https://doi.org/10.2174/1568009618666180905100608Test http://eurekaselect.com/article/download/165126Test |
| رقم الانضمام: | edsbas.7138ABF9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.2174/1568009618666180905100608 |
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