Hematopoiesis derived from iPS lines with an aged hematopoietic progenitor origin display multiple young functional characteristics. (A) Ratios of the peripheral lineage distribution in individual chimeric animals derived from young and aged BiPS lines. Chimeric ratios are depicted as previously described26,27 for both blastocyst derived (B) and iPS derived (i) hematopoiesis. Numbers above bars denote individual mice, whose total blood cell chimerism can be found in supplemental Table 2. (B) The frequency of HSCs among lineage negative Sca-1 positive c-kit positive BM cells in steady-state young and aged mice (3 independent experiments, 6 and 9 mice, respectively), and among blastocyst- and agedBiPS-derived lineage negative Sca-1 positive c-kit positive BM cells in primary chimeras (3 independent experiments, totaling 8, 3, and 5 mice, respectively). (C) Competitive repopulating ability of young, aged, agedBiPS1, and agedBiPS2 HSCs assessed as the ability of each transplanted HSC to repopulate the peripheral myeloid compartment of lethally irradiated young recipients 16 weeks posttransfer (3 independent experiments, n = 5, 25, 12, and 25 mice per group, respectively). (D) In vivo lineage distribution after transplantation of young and aged BiPS HSCs into lethally irradiated young recipients. Analysis was performed (as in A). (E) The ability of transplanted young, aged, blastocyst, agedBiPS1, and agedBiPS2-derived HSCs to generate naïve TREC+ T cells in repopulated recipient mice (from 2 independent experiments, totaling 4, 4, 10, 3, and 7 mice, respectively). Bars depict mean ± SEM.
