Cell-autonomous basis of multilineage hematopoietic defects after Men1 inactivation. (A) Experimental design. CD45.2⁺ BM was harvested from CreER^Tm+Men1^f/f or control CreER^Tm−Men1^f/f mice (CD45.2⁺) without prior TAM, mixed at a 1:1 ratio with competitor CD45.1⁺ BM and transplanted into lethally irradiated B6.SJL mice. After 12 weeks to establish mixed chimerism, TAM was administered. (B) The contribution of CD45.2⁺ cells to blood myeloid (Gr1⁺CD11b⁺), B (B220⁺CD19⁺), and T (Thy1.2⁺) cells was assessed before administration of TAM and 2, 6, 10, and 16 weeks thereafter. Results are shown as mean plus or minus SEM and normalized to the chimerism observed at baseline. ▵: CD45.1⁺ competitor and CD45.2⁺CreER^Tm−Men1^f/f; ▴: CD45.1⁺ competitor and CD45.2⁺CreER^Tm+Men1^f/f. (C) Contribution of CD45.2⁺ cells (% + SEM) to the BM LT-HSC compartment (CD150⁺CD48⁻LSK cells), other LSK progenitors containing short-term HSCs, CMPs, and GMPs 16 weeks after TAM administration. (D) Relative contribution of CD45.2⁺ cells to the CD150⁺CD48⁻LSK BM LT-HSC compartment in a group of mice transplanted as described in panel A, followed by challenge with 5-FU. Data were acquired 16 days after 5-FU injection. Results were normalized to the chimerism in the control group. * indicates statistical significance (P < .05).