HSCs of SPARC-deficient mice return to quiescence faster after 5-FU treatment. (A) FACS plot and quantification of time course of Ki67/Hoechst cell cycle analysis of HSCs (Lin⁻Sca-1⁺CD48⁻CD150⁺CD34⁻) of WT and Sparc^−/− mice after 5-FU treatment (N = 12 per group and time point; mean and SD). c-Kit was omitted from the gating strategy as c-Kit expression drops after 5-FU treatment.⁷  (B) WT and Sparc^−/− mice: percentage of HSCs in G₀ phase of cell cycle at homeostasis and at different time points after 5-FU treatment (N = 12 per group and time point; mean and SD; ****P < .001; unpaired 2-tailed Student t test). In SPARC-deficient mice, HSCs return to quiescence more rapidly following 5-FU treatment. (C) WT and Sparc^−/− mice: percentage of BrdU⁺ HSCs at homeostasis and at different time points after 5-FU treatment (N = 6 per group and time point; mean and SD; *P < .05; ****P < .001; unpaired 2-tailed Student t test). (D) Survival curve of WT and Sparc^−/− mice treated with 5-FU at a dose of 150 μg/g at 7-day intervals (N = 10 per group; median survival: WT = 15.5 days, Sparc^−/− = 17 days; no significant difference; log-rank [Mantel-Cox] test and Gehan-Breslow-Wilcoxon test). Time points of 5-FU injections are indicated with arrows. (E) Survival curve of WT and Sparc^−/− mice treated with 5-FU at a dose of 150 μg/g at 11-day intervals (N = 13-14 per group; median survival: WT = 52.5 days, Sparc^−/− = 79 days; ****P < .001; log-rank [Mantel-Cox] test and Gehan-Breslow-Wilcoxon test).