Figure 4
Figure 4. Noncompetitive transplantation of Notch-activated HSPCs leads to hematopoietic failure. (A) Lethally irradiated CD45.1+ congenic mice were reconstituted with 5-FU–treated donor CD45.2+Rag1−/− BM cells transduced with MigR1 control or activated Notch1. At 6 weeks after transplantation, CD45.2+GFP+Lineage−Sca-1+c-Kit+ cells (HSPCs) were sorted and transplanted into CD45.1+ hosts at 500 cells per mouse. (B) Kaplan-Meier graph showing the proportion of mice alive after transplantation. (C) Scatter plot analysis of moribund mice at 11 days after transplantation showing peripheral blood hemoglobin concentration; absolute numbers of total donor-derived (CD45.2+GFP+) splenocytes, splenic ter119+ erythroid cells, splenic CD11b+ myeloid cells, Thy-1+ T cells, splenic Lineage−Sca-1+c-Kit+ HSPCs, and splenic Lineage−Sca-1−c-Kit+CD34+CD16/62hi granulocyte-macrophage progenitors (GMPs); and day 11 CFU-S colonies. The experiment was performed twice; 4 mice for MigR1 and 9 mice for activated Notch1.

Noncompetitive transplantation of Notch-activated HSPCs leads to hematopoietic failure. (A) Lethally irradiated CD45.1+ congenic mice were reconstituted with 5-FU–treated donor CD45.2+Rag1−/− BM cells transduced with MigR1 control or activated Notch1. At 6 weeks after transplantation, CD45.2+GFP+LineageSca-1+c-Kit+ cells (HSPCs) were sorted and transplanted into CD45.1+ hosts at 500 cells per mouse. (B) Kaplan-Meier graph showing the proportion of mice alive after transplantation. (C) Scatter plot analysis of moribund mice at 11 days after transplantation showing peripheral blood hemoglobin concentration; absolute numbers of total donor-derived (CD45.2+GFP+) splenocytes, splenic ter119+ erythroid cells, splenic CD11b+ myeloid cells, Thy-1+ T cells, splenic LineageSca-1+c-Kit+ HSPCs, and splenic LineageSca-1c-Kit+CD34+CD16/62hi granulocyte-macrophage progenitors (GMPs); and day 11 CFU-S colonies. The experiment was performed twice; 4 mice for MigR1 and 9 mice for activated Notch1.

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