c-Myc is required for endomitosis and polyploidy differentiation but is not essential for megakaryocyte maturation. (A) c-Myc^−/− megakaryocytes are smaller than WT megakaryocytes as shown by flow cytometry forward scatter. (B,C) c-Myc^−/− megakaryocytes have lower ploidy, as shown by propidium iodide staining. The appearance of the sub-G₁ population in the c-Myc^−/− CD41⁺ population suggests increased apoptosis in c-Myc^−/− megakaryocytes. A typical representative of 3 separate experiments is shown. (D) Comparison of the absolute number of low-ploidy (< 8N), medium ploidy (8-32N), and high ploidy (> 32N) in BM plus spleens of c-Myc^−/− and WT control mice. (E) Cylin D1 and D2 expression is down-regulated in c-Myc^−/− MK-Ps (lin⁻Sca1⁻c-kit⁺Cd41⁺) compared with WT counterparts. (F) Increased apoptosis of CD41⁺ megakaryocytes as shown by annexin-V staining. (G) Down-regulation of pro-survival genes Bcl-2 and Mcl1 in CD41⁺ megakaryocytes of c-Myc^−/− mice compared with WT controls. (H) Expression of mature megakaryocytic markers in c-Myc^−/− megakaryocytes (CD41⁺c-kit⁻) compared with that of WT counterparts. **P < .01.