Defective cell-intrinsic hematopoietic stem cell function after induced expression of Ezh2^Y641F. (A) Total BM cellularity in Mx1-Cre Ezh2^Y641F mice and Mx1-Cre control mice (n = 5 per group). (B) CLP counts in BM of Mx1-Cre Ezh2^Y641F and Mx1-Cre–only control mice (n = 5). (C) Analysis of KSL and MP populations. (D) Representative flow cytometry plots of BM hematopoietic progenitor populations. (E) Image of tibiae from a Mx1-Cre Ezh2^Y641F mouse (right) and control (left). (F) Hematoxylin and eosin (H&E)–stained bone sections from Mx1-Cre Ezh2^Y641F (bottom) and Mx1-Cre control mice (top). (G) Target allele recombination from DNA isolated from the bone and BM of the indicated genotypes. (H) Number of Cre⁺ osteocytes in bone sections from Mx1-Cre^– and Mx1-Cre⁺ mice (n = 4). (I) Representative IHC image for Cre protein in Mx1-Cre⁺ bone sections. Yellow arrows indicate Cre⁺ osteocytes. (J) Workflow for competitive BM transplant assay with the indicated genotypes. (K-L) Donor cell contribution to peripheral blood chimerism before (K) and after induction (L) of Ezh2^Y641F expression by poly(I:C) (n = 8 mice per group). Error bars represent standard deviation. P values as indicated, multiparameter t test. BM, bone marrow; CLP, common lymphoid progenitor; KSL, ckit⁺ Sca1⁺ lineage-negative; MP, myeloid progenitor; rec, recombination; WT, wild-type.