Parp-2 is required for efficient erythropoiesis in mice by limiting replicative stress in erythroid progenitors

Erythropoiesis is a tightly regulated process in which multipotential hematopoietic stem cells give rise to mature red blood cells. Here, we show that Parp-2 deficiency in mice leads to chronic anemia, despite increased EPO plasma levels, providing a novel role for Parp-2 in erythropoiesis. Loss of Parp-2 causes shortened red blood cells lifespan and impaired differentiation of erythroid cells. Transcriptomic analyses revealed the activation of the p53-dependent-DNA damage response pathways on Parp-2-deficient erythroblasts, triggering the expression of genes involved in cell cycle checkpoints and apoptosis. Accordingly, Parp-2-deficient erythroblasts shows G2/M cell cycle arrest and increased apoptosis. 4 samples were analyzed: Parp-2-/- (n=2); WT (n=2)