Human hematopoietic stem/progenitor cells display ROS-dependent long-term hematopoietic defects after exposure to low dose of ionizing radiations

Hematopoietic stem cells are responsible for life-long blood cell production and are highly sensitive to exogenous stresses. The effects of low doses of ionizing radiations on radiosensitive tissues such as the hematopoietic tissue remain unknown despite their increasing use in medical imaging. Here, we study the consequences of low doses of ionizing radiations on differentiation and self-renewal capacities of human primary hematopoietic stem/progenitor cells. We find that a single 20mGy dose impairs hematopoietic reconstitution potential of human hematopoietic stem/progenitor cells but not their differentiation properties. Contrary to high irradiation doses, low doses of irradiation do not induce DNA double strand breaks in hematopoietic stem/progenitor cells but, similar to high doses, induce a rapid and transient increase of ROS that promotes activation of the p38MAPK pathway. Hematopoietic stem/progenitor cell treatment with ROS scavengers or p38MAPK inhibitors prior exposure to 20mGy irradiation abolishes the 20mGy-induced defects indicating that ROS and p38MAPK pathways are transducers of low doses of radiation effects. Altogether these results show that a 20mGy dose of ionizing radiations reduces reconstitution potentials of hematopoietic stem/progenitor cells suggesting an effect on self-renewal potential of human hematopoietic stem cells and pinpoint ROS or the p38MAPK as therapeutic targets which inhibition enables to protect human primary hematopoietic stem/progenitor cells from low dose irradiation toxicity.