Figure 1.

MEK1 Ablation Increases HSC Proliferation and Differentiation, Leading to HSC Exhaustion

(A) Serial transplantation protocol.

(B and C) Blood chimerism (left), lineage distribution (center) in peripheral blood, BM cellularity, and HSC chimerism in lethally irradiated recipients reconstituted with F/F, CRE+, or cKO BM analyzed during the first (B) or second (C) round of transplantation.

(D) Repetitive (rep) 5-FU treatment protocol.

(E) HSCs per femur, lineage+ cells per femur, and peripheral blood parameters (Hb, hemoglobin; PLT, platelets; WBC, white blood cells) during repetitive 5-FU treatment.

(F) Kaplan-Meier survival curve. Median survival time (MST): F/F = 84 days; MEK1-cKO = 39 days; p < 0.001 according to the log rank (Mantel-Cox) test.

(G) Colony-forming units (CFUs) and % lineage+ cells derived from HSCs in LTC.

(H) Cell cycle distribution of HSCs harvested 12 weeks after transplantation (Transpl), 12 days after the third 5-FU injections (rep 5-FU), or after 6 weeks in LTC.

Error bars represent the SD of the mean. ^∗p < 0.05, ^∗∗p < 0.01, and ^∗∗∗p < 0.001 comparing CRE+ or F/F to cKO. See also Figure S1.