An early pre-liver intraembryonic source of CFU-S in the developing mouse

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Abstract
IT is widely accepted that during murine embryogenesis, totipotent haematopoietic stem cells first originate in the yolk sac, then migrate to the fetal liver and finally colonize the bone marrow shortly before birth1,2. This view is based on in vitro studies showing that yolk sac cells can differentiate into various haematopoietic lineages1,3–7 and in vivo studies showing that yolk sac contains spleen colony-forming units (CFU-S) beginning at day 8 of gestation1. However, some investigators have failed to find statistically significant numbers of CFU-S arising from day 9 yolk sac3,8–11 and, although one group reported that yolk sac could repopulate the haematopoietic system of W mutant mice2, others have failed to confirm yolk sac-derived repopulation of adults3,12. In the avian and amphibian systems, the yolk sac gives rise only to early, transitory haematopoiesis whereas the definitive adult haematopoietic stem cells in these vertebrates are derived from the mesodermal region containing the dorsal aorta13–17. Because this analogous area of the mouse embryo has not been previously examined for haematopoietic activity, we directly compared the CFU-S activity of the aorta, gonad, mesonephros (AGM) region with the yolk sac and fetal liver during embryogenesis. Here we report that this intra-embryonic AGM region contains CFU-S activity at a higher frequency than that in embryonic yolk sac and that such activity appears in the AGM region before the fetal liver.