Low-dose niraparib treatment leads to DNA damage in MKs and MkPs and enhances MK maturation. Mice were treated with 25 mg/kg niraparib or vehicle control. (A) γH2AX positivity in indicated HSPC populations in vehicle- or niraparib-treated mice (n = 5 mice per group). Data shown as mean ± SD; 1-way ANOVA with Dunnett post hoc test. Gating strategy shown in supplemental Figure 2. (B) Representative widefield images of femoral cryosections derived from vehicle- or niraparib-treated mice (CD41, green; γH2AX, purple; scale bar, 20 μm). Quantification shows the percentage of femoral MKs that have either 0, 1 to 10, or >10 γH2AX foci in the nucleus; 100 MKs counted per femur (n = 3 mice per group). Data shown as mean ± SD; multiple t tests. (C) Representative images of native MKs from vehicle- or niraparib-treated mice (left; green, SYBR gold; scale bars, 100 μm). MKs were isolated from femurs and the tail DNA (%) of at least 120 MKs per femur were analyzed across 3 replicates (3 femurs) per condition (n = 3 mice per group). Violin plots show distribution of all data points along with median and interquartile range; unpaired, 2-tailed Student t test. (D) Ploidy distribution in native MKs from vehicle- or niraparib-treated mice after 3 and 11 days (n = 5 mice per group). Data shown as mean ± SD; 2-way ANOVA with Šidák correction used for multiple comparisons. DMSO, dimethyl sulfoxide; ST-HSC, short-term HSC.