N-Ras^G12Dand Tet2 haploinsufficiency collaborate to enhance HSC competitiveness and self-renewal. (A) Donor (CD45.2) BM cells (5 × 10⁵) from Mx1-Cre/Nras^G12D/+, Mx1-Cre/Tet2^+/−, Mx1-Cre/Nras^G12D/+/Tet2^+/−, and littermate control mice at 2 weeks after poly (I:C) treatment (n = 3 donors per genotype) were transplanted into lethally irradiated recipient (CD45.1) mice (n = 15 recipients per genotype) along with 1.5 × 10⁶ recipient BM cells. Donor-cell reconstitution in total nucleated cells and myeloid (Mac1⁺Gr1^low and Mac1⁺Gr1⁺) and B- (B220⁺) and T-cell (CD3⁺) lineages was assessed in peripheral blood for 4 to 20 weeks after transplantation. (B) BM percentages of donor-derived HSCs (CD150⁺CD48⁻LSK), MPPs (CD150⁻CD48⁻LSK), and LSKs (Lin⁻Sca1⁺c-Kit⁺) and donor-derived myeloid (Mac1⁺Gr1^low and Mac1⁺Gr1⁺) and B- (B220⁺) and T-cell (CD3⁺) lineages in primary transplant recipients (n = 8 per genotype). (C) Secondary transplantation (n = 10 recipients per genotype) of 3 × 10⁶ BM cells from primary recipient mice in panel A (n = 2 donors per genotype). Donor-cell reconstitution in total nucleated cells and myeloid and B- and T-cell lineages was assessed. (D) Donor-derived myeloid and B- and T-cell lineages in the BM of secondary recipient mice (n = 9 per genotype). Data represent mean ± standard error of the mean. Two-tailed Student t tests were used to assess statistical significance. *P ≤ .05, **P ≤ .01, ***P ≤ .001.