Figure 4
Figure 4. Markedly impaired function of menin-deficient hematopoietic stem cells after competitive transplantation. (A) Experimental design. BM was harvested from TAM-treated CreERTm+ Men1f/f or CreERTm− Men1f/f mice (CD45.2+). CD45.1+ competitor B6.SJL BM cells were mixed with an increasing number of CD45.2+ tester cells (1:1, 1:3, 1:9 ratios) and used to reconstitute lethally irradiated B6.SJL mice. (B) Contribution of CD45.2+ and CD45.1+ cells to blood Gr1+CD11b+ myeloid cells 16 weeks after transplantation. Representative examples are shown. (C) Percentage of CD45.2+ cells in blood myeloid cells at 16 weeks for each recipient (triangles) in 1 representative experiment. Similar data were obtained in 4 independent experiments. (D) Impaired repopulation of the long-term HSC compartment by menin-deficient progenitors. BM was analyzed 10 months after transplantation. A representative example is shown for recipients of a 1:3 competitor:tester ratio. Long-term HSCs were identified among LSK progenitors using SLAM markers, as follows: CD150+CD48−Lin–Sca-1hic-kithi cells.24

Markedly impaired function of menin-deficient hematopoietic stem cells after competitive transplantation. (A) Experimental design. BM was harvested from TAM-treated CreERTm+Men1f/f or CreERTmMen1f/f mice (CD45.2+). CD45.1+ competitor B6.SJL BM cells were mixed with an increasing number of CD45.2+ tester cells (1:1, 1:3, 1:9 ratios) and used to reconstitute lethally irradiated B6.SJL mice. (B) Contribution of CD45.2+ and CD45.1+ cells to blood Gr1+CD11b+ myeloid cells 16 weeks after transplantation. Representative examples are shown. (C) Percentage of CD45.2+ cells in blood myeloid cells at 16 weeks for each recipient (triangles) in 1 representative experiment. Similar data were obtained in 4 independent experiments. (D) Impaired repopulation of the long-term HSC compartment by menin-deficient progenitors. BM was analyzed 10 months after transplantation. A representative example is shown for recipients of a 1:3 competitor:tester ratio. Long-term HSCs were identified among LSK progenitors using SLAM markers, as follows: CD150+CD48Lin–Sca-1hic-kithi cells.24 

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