M40^−/− mice are more resistant to cytotoxic stress and M40^−/− HSPCs show superior regenerative ability upon stress. (A) Kaplan-Meier survival curve of WT and M40^−/− mice after weekly administration of 5-FU (150 mg/kg). Data from 2 independent experiments are pooled and shown here; n = 13 per genotype. P < .01, log-rank nonparametric test comparing WT and M40^−/− groups. (B) CFC numbers per 8 × 10⁴ BM cells 1 day after 5-FU injection were quantified in semisolid methylcellulose media with cytokines (M3434; Stemcell Technologies Inc). (C) Frequency of phenotypic LT-HSCs (CD34⁻CD150⁺CD48⁻LSK) at day 7 following single injection of 5-FU. P value was calculated by the Student t test. Dotted red line represents the frequency of steady-state LT-HSCs. (D) Representative histograms depicting BrdU incorporation in SLAM LSK cells 7 days after 1 single 5-FU injection are shown. BrdU was injected 2 hours prior to BM harvest. BrdU⁺ fractions were quantified (mean ± SE). *P < .05 as determined by the Student t test. (E) Colony numbers per 8 × 10⁴ BM cells (left), total BM cells (middle), and total colony numbers in the BM (right) 10 days after 5-FU injection (ie, 3 days after the second 5-FU injection) are shown. P values were calculated by the 2-tailed Student t test. SE, standard error.