Figure 2.
Elderly Gata2 haploinsufficient HSCs have a functional defect in reconstitution of multilineage hematopoietic compartments with a myeloid bias. (A) Schematic representation of competitive HSC transplantation experiment. Three hundred HSCs from aged control or Gata2+/fl; Vav-iCre+ mice (CD45.2+) together with 2 × 105 unfractionated BM competitor cells (CD45.1+) were transplanted into lethally irradiated (9.5 Gy) recipient mice (CD45.1+). Four independent biological replicates were used for each genotype. Donor chimerism in PB was tested every 4 weeks until week 16 after transplant. (B) Proportion of CD45.2 donor-derived cells in PB after transplantation of donor cells from control (n = 8 recipients) or Gata2+/fl; Vav-iCre+ mice (n = 8 recipients). (C-E) Percentages of CD45.2 donor-derived cells contribution to mature cells in PB (C) BM HSPCs (D) and BM committed myeloid/lymphoid progenitors (E) at week 16 after transplantation of control or Gata2+/fl; Vav-iCre+ donor cells. n = 8 recipients for each genotype from 2 independent experiments. (F) Fold change ratios of CD45.2 donor-derived cell contribution to mature PB cells in aged mice (n = 8 control and 8 Gata2+/fl; Vav-iCre+) in relation to young mice (n = 8 control and 8 Gata2+/fl; Vav-iCre+) donor cells after normalizing to their control counterparts. 2 to 3 independent experiments were performed for each condition. Data is presented as mean ± SEM. Statistical analysis is performed using the Mann-Whitney U test. Significant data: *P < .05; **P < .01; ***P < .001.

Elderly Gata2 haploinsufficient HSCs have a functional defect in reconstitution of multilineage hematopoietic compartments with a myeloid bias. (A) Schematic representation of competitive HSC transplantation experiment. Three hundred HSCs from aged control or Gata2+/fl; Vav-iCre+ mice (CD45.2+) together with 2 × 105 unfractionated BM competitor cells (CD45.1+) were transplanted into lethally irradiated (9.5 Gy) recipient mice (CD45.1+). Four independent biological replicates were used for each genotype. Donor chimerism in PB was tested every 4 weeks until week 16 after transplant. (B) Proportion of CD45.2 donor-derived cells in PB after transplantation of donor cells from control (n = 8 recipients) or Gata2+/fl; Vav-iCre+ mice (n = 8 recipients). (C-E) Percentages of CD45.2 donor-derived cells contribution to mature cells in PB (C) BM HSPCs (D) and BM committed myeloid/lymphoid progenitors (E) at week 16 after transplantation of control or Gata2+/fl; Vav-iCre+ donor cells. n = 8 recipients for each genotype from 2 independent experiments. (F) Fold change ratios of CD45.2 donor-derived cell contribution to mature PB cells in aged mice (n = 8 control and 8 Gata2+/fl; Vav-iCre+) in relation to young mice (n = 8 control and 8 Gata2+/fl; Vav-iCre+) donor cells after normalizing to their control counterparts. 2 to 3 independent experiments were performed for each condition. Data is presented as mean ± SEM. Statistical analysis is performed using the Mann-Whitney U test. Significant data: *P < .05; **P < .01; ***P < .001.

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