Heterogeneous cellular expansion induced by Tet2 KO. (A) Experimental workflow. HSCs from Rosa26-Cre^ERT2+/−Tet2^fl/fl mice and Rosa26-Cre^ERT2–/–Tet2^fl/fl littermate mice were barcoded and transplanted into wild-type recipients. Tet2 KO was induced 1 month after transplantation via tamoxifen injection. The experiment was performed twice. The combined results of 4 control mice and 6 Tet2 KO mice are shown. (B) Peripheral blood analysis via fluorescence-activated cell sorting (FACS). The abundance of B cells and granulocytes in control and Tet2 KO mice are shown. Error bars represent SEM. Two-tailed t test. (C) FACS analysis of HSPCs at the end point, 13 months after transplantation. Bars show the mean of control and Tet2 KO groups. Two-tailed t test. (D) The clonal abundance of the top 15 most abundant clones in each mouse. Each dot represents 1 clone. Bars show the median of the control and Tet2 KO groups. Control clones n = 60 and Tet2 KO clones n = 90. Two-tailed Mann-Whitney U test. (E-G) Distribution of granulocyte clonal abundance in the peripheral blood (PB) (E) and distribution of MPP3 (F) and HSC (G) clonal abundance in the BM. The bottom x-axis denotes the percent of unique clones in respective groups shown as bars. The top x-axis denotes the total abundance as a percent of the corresponding cell type for each bar shown as red dots. Green highlights bars that represent high-abundance clones are only found in the Tet2 KO group. Shown are clones from all mice in each group. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001. BM, bone marrow; CMP, common myeloid progenitor; GMP, granulocyte-monocyte progenitor; MEP, megakaryocyte–erythroid progenitor; MNC, mononuclear cell; SEM, standard error of mean; WBCs, white blood cells.