Dok1 and Dok2 proteins regulate cell cycle in hematopoietic stem and progenitor cells
Résumé
Dok1 and Dok2 proteins play a crucial role in myeloid cell proliferation as demonstrated by Dok1 and Dok2 gene inactivation, which induces a myeloproliferative disease in aging mice. In this study, we show that Dok1/Dok2-deficiency affects myeloproliferation even at a young age. An increase in the cellularity of multipotent progenitors (MPP) is observed in young Dok1/Dok2-deficient mice. This is associated with an increase in the cells undergoing cell cycle, which is restricted to myeloid committed progenitors. Furthermore, cellular stress triggered by 5-Fluoro Uracil (5-FU) treatment, potentiates the effects of the loss of Dok proteins on MPP cell cycle. In addition, Dok1/Dok2 deficiency induces resistance to 5-FU induced hematopoietic stem cell (HSC) exhaustion. Taken together, these results demonstrate that Dok1 and Dok2 proteins are involved in the control of HSC cell cycle regulation.