Hippo kinase inactivation promotes macrothrombocytopenia upon aging, even in the absence of malignant clonal HSC expansion. Genotypes analyzed for this figure include Stk4^f/fStk3^f/f;Vav1-Cre⁺ (Stk4^−/−Stk3^−/−, red), Stk4^f/+Stk3^f/+;Vav1-Cre⁺ (Stk4^+/−Stk3^+/−, blue), and Stk4^f/fStk3^f/f;Vav1-Cre⁻ (Stk4^+/+Stk3^+/+, green). Primary transplantations: n = 10 (Stk4^+/+Stk3^+/+), n = 10 (Stk4^+/−Stk3^+/−), and n = 9 (Stk4^−/−Stk3^−/−). Secondary transplantations: n = 8 (Stk4^+/+Stk3^+/+) and n = 8 (Stk4^+/−Stk3^+/−). (A-D) Donor-derived frequencies (CD45.2%) in the peripheral blood over the course of primary and secondary bone marrow transplantations are shown for total mononuclear cells (A), myeloid-lineage cells (CD11b⁺) (B), B-lineage cells (B220⁺) (C), and T-lineage cells (CD3⁺) (D). (E) Analysis of hematopoietic stem/progenitor cell donor–derived frequencies (CD45.2%) in total bone marrow at the experimental end point (48 weeks). Total cell counts for the indicated populations are shown (left axis). Mean donor- and recipient-derived frequencies are indicated as a percentage. Statistical significance was determined by 2-tailed Student t test. (F) Platelet count and MPV peripheral blood of mice receiving the indicated donor genotypes at 40 weeks after transplant. Data are presented as the mean ± SEM. Statistical significance was determined by 2-tailed Student t test. *P < .05, **P < .01, ***P < .001.