Cell-intrinsic defects in c-Myc^−/− HSC/Ps. (A-E) A total of 2 × 10⁶ BM cells from c-Myc^−/− mice (before c-Myc deletion was induced) and WT control mice were transplanted into lethally irradiated recipient mice separately. Six weeks after transplantation, at which point hematopoiesis was completely regenerated in the recipient mice by donor HSCs, recipient mice were injected with poly I:C to induce c-Myc deletion. The hematopoietic phenotypes of recipient mice were analyzed one month after poly I:C injection. (A) Thrombocytosis and anemia developed in recipient mice receiving c-Myc^−/− BM hematopoietic cells. (B-C) Increased megakaryocytosis in the spleens of recipient mice receiving c-Myc^−/− BM cells, as shown by AChE staining (20×/.7 air). (D-E) Increased Lin⁻ cell population (D), as well as Lin⁻CD41⁺c-Kit⁺ and Lin⁻CD41⁺c-Kit⁻ megakaryocytes (E) in BM of mice receiving c-Myc^−/− BM hematopoietic cell transplantation, as shown by flow cytometric analysis. (F) Equal numbers of c-Myc^−/− BM cells (before c-Myc deletion was induced, CD54.2⁺ background) and competitor BM cells (CD54.1⁺ background) were transplanted into lethally irradiated recipient mice (CD54.1⁺ background). One month after transplantation, recipient mice were injected with poly I:C to induce c-Myc deletion. The percentages of CD41⁺ and Gr1⁺ cells in CD45.1⁺ population (competitor BM cell-derived) or CD45.2⁺ (c-Myc^−/− BM-derived) population were examined, respectively, by flow cytometry. (G-I) Colony-forming units in spleen (CFU-S) generated by c-Myc^−/− HSC/Ps (G) are enriched for CD41⁺ megakaryocytes, as shown by flow cytometric analysis (H) and AChE staining (I). **P < .01.