Fig. 8: ROS-mediated DNA damage causes dysfunction of LT-HSCs. | Nature Communications

Fig. 8: ROS-mediated DNA damage causes dysfunction of LT-HSCs.

From: Mutant ASXL1 induces age-related expansion of phenotypic hematopoietic stem cells through activation of Akt/mTOR pathway

Fig. 8: ROS-mediated DNA damage causes dysfunction of LT-HSCs.The alternative text for this image may have been generated using AI.

a The experimental design for transplantation using whole bone marrow cells treated with an antioxidant scavenger NAC. Whole bone marrow cells isolated from young control and young Vav-Cre ASXL1-MT KI mice that had been treated with NAC for 8 weeks were transplanted into lethally irradiated recipient mice with competitor cells. Recipient mice were continuously treated with NAC after transplantation. b, c 6 weeks after transplantation, effects of NAC administration on ROS (b) and γ-H2AX levels (c) in LSK cells were determined (n = 4 (NAC−) and 5 (NAC+)). d, e The frequencies of donor-derived cells (d) and CD11b-positive cells in donor-derived cells (e) in peripheral blood were analyzed (n = 8 (Control-NAC−), 6 (Control-NAC+), 6 (ASXL1-MT-NAC−), and 8 (ASXL1-MT-NAC+)). f The experimental design for transplantations using Lin− cells transduced with ROS-detoxifying enzymes. Lin− cells from young Vav-Cre ASXL1-MT KI mice transduced with control or Catalase-SOD2 retrovirus were transplanted into lethally irradiated recipient mice. g Engraftment was assessed at the indicated weeks after transplantation (n = 7 (Mock) and 8 (Catalase-SOD2)). Data are mean ± s.e.m. Statistical significances are assessed by two-tailed Student’s t-test. *P ≤ 0.05, **P ≤ 0.01.

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