Ionizing radiation-induced expression of INK4a/ARF in murine bone marrow-derived stromal cell populations interferes with bone marrow homeostasis
Menée sur un modèle murin, cette étude identifie un mécanisme par lequel des rayonnements ionisants sont susceptibles de perturber l'homéostasie de la moelle osseuse
Alterations of the bone marrow microenvironment have been shown to occur after chemoradiotherapy during aging and following genetic manipulations of telomere length. Still, whether marrow stromal cells are adopting senescent features in response to these events is unknown. Here, we show evidence that exposure to ionizing radiation (IR) leads murine stromal bone marrow cells to express senescence markers, namely senescence-associated β-galactosidase and increased p16INK4a/p19ARF expression. Long-term (8 weeks) after exposure of mice to IR, we observed a reduction in the number of stromal cells derived from bone marrow aspirates (referred as BM-SC) an effect we found was absent in irradiated ink4a/arf knockout mice and mostly independent on the colony forming unit potential of the stroma. Such reduction in the number of BM-SC was specific as stromal cells isolated from collagenase treated bone (referred as OB-SC) were not reduced post IR. Surprisingly, we found exposure to IR leads to a cellular non-autonomous and ink4a/arf dependent effect on lymphopoiesis. Overall, our results reveal distinct sensitivity of marrow stromal cell populations to IR and suggest that long-term residual damage to the bone marrow microenvironment can influence hematopoiesis in an ink4a/arf dependent manner.
Blood 2011