Aged Moz-deleted Moz^fl/fl;Mx1-cre bone marrow cells acquire long-term reconstitution capability. (A) Experimental design. Mice were treated with poly(I:C) and then left undisturbed for 15 months prior to transplantation. Peripheral blood was analyzed at 4.3 months after transplantation. (B) Contribution to peripheral blood leukocytes 4.3 months after transplantation, both in the presence of 8-week-old wild-type competitor bone marrow and without competitor (noncompetitive). Note that aged Moz^fl/fl control HSCs still have efficient multilineage reconstituting capacity. (C-D) Comparison of contribution of Moz-intact Moz^fl/fl or Moz-deleted Moz^fl/fl;Mx1-cre transplant to circulating B cells, T cells, myeloid cells, and total white blood cells (WBCs) after transplantation with (C) competitor and (D) without competitor presented as a percentage of CD45.2 (donor) contribution to peripheral blood. (C) Note that Moz-deleted bone marrow contains myeloid repopulating activity, but almost completely lacks lymphoid repopulating activity in competitive transplants. (D) However, the same cell preparations produce extensive multi-lineage contribution in the absence of exogenous competitor. (E) PCR genotyping of myeloid colonies from cultures sorted from the bone marrow of recipients analyzed in D. (E) Genotyping of Moz-intact Moz^fl/fl or Moz-deleted Moz^fl/fl;Mx1-cre progenitor colonies grown from cells isolated from transplant recipients. CD45.2 (donor) cells were isolated by FACS from primary recipients and cultured in the presence of SCF, EPO, and IL3 (supplemental Figure 10). Examples showing genotyping of large colonies derived from highly proliferative progenitors originally derived from control Moz^fl/fl or Moz^fl/fl;Mx1-cre mice treated with poly(I:C) almost 2 years earlier. Note that colonies from Moz^fl/fl;Mx1-cre contain Moz deleted alleles (Figure 1G). Data are presented as the mean ± SEM.