Fig. 3. p53R248W/+ confers a survival advantage to HSPCs after radiation.
a BM chimeras were generated by transplanting a 1:10 ratio of p53R248W/+ cells (CD45.2+) to p53+/+ cells (CD45.1+) into irradiated recipient mice (CD45.1+CD45.2+). After hematopoietic reconstitution (8 weeks), mice were treated with or without 5 gray (Gy) total body irradiation (TBI). b Percentage of p53R248W/+ (CD45.2+) cells in PB of recipient mice following TBI treatment; n = 7 mice per group. c Percentage of p53R248W/+ cells (CD45.2+) in the BM of recipient mice at 16 weeks following TBI treatment; n = 7 mice per group. d Percentage of p53R248W/+ LSK cells (CD45.2+) in the BM of recipient mice at 16 weeks following TBI treatment; n = 7 mice per group. e Hematopoietic stem and progenitor cells from p53+/+ and p53R248W/+ mice were assessed for apoptosis 2 h after 2 Gy TBI; n = 3 mice per group. f HSCs purified from the BM of p53+/+ and p53R248W/+ mice were treated with 2 Gy TBI and then assessed for apoptosis; n = 3 mice per group. g Competitive transplantation assays using BM cells isolated from p53+/+ and p53R248W/+ mice treated with 2 Gy TBI. Two hours following TBI, we isolated BM cells from irradiated mice and transplanted 500,000 live BM cells together with equal number of competitor BM cells into lethally irradiated recipient mice. The percentage of donor-derived cells in the PB of recipient mice; n = 7–8 mice per group. h Percentage of donor-derived LT-HSCs, ST-HSCs, MPPs, and LSK cells in the PB of the primary recipient mice 16 weeks following transplantation; n = 7–8 mice per group. i Contribution of p53+/+ and p53R248W/+ BM cells to recipient mouse PB in secondary transplantation assays; n = 5–7 mice per group. j Lineage contribution of donor-derived cells in the PB of secondary recipient mice 16 weeks following transplantation; n = 5–7 mice per group. Data are represented as mean ± SEM. P-values were calculated using two-way ANOVA with Bonferroni’s multiple comparisons test in b, e, g, i, and j, unpaired t-test with Welch’s correction in c, d, f, and h; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Source data are provided as a Source Data file.