Medvinsky A L, Samoylina N L, Müller A M, Dzierzak E A
Laboratory of Physiology of Hematopoiesis, National Research Centre for Hematology, Moscow, Russia.
Nature. 1993 Jul 1;364(6432):64-7. doi: 10.1038/364064a0.
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 birth. This view is based on in vitro studies showing that yolk sac cells can differentiate into various haematopoietic lineages and in vivo studies showing that yolk sac contains spleen colony-forming units (CFU-S) beginning at day 8 of gestation. However, some investigators have failed to find statistically significant numbers of CFU-S arising from day 9 yolk sac and, although one group reported that yolk sac could repopulate the haematopoietic system of W mutant mice, others have failed to confirm yolk sac-derived repopulation of adults. In the avian and amphibian systems, the yolk sac gives rise only to early, transitory haematopoiesis whereas the definite adult haematopoietic stem cells in these vertebrates are derived from the mesodermal region containing the dorsal aorta. 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.
人们普遍认为，在小鼠胚胎发生过程中，全能造血干细胞首先起源于卵黄囊，然后迁移至胎儿肝脏，最终在出生前不久定植于骨髓。这一观点基于体外研究显示卵黄囊细胞可分化为多种造血谱系，以及体内研究显示从妊娠第8天开始卵黄囊中就含有脾集落形成单位（CFU-S）。然而，一些研究人员未能在第9天的卵黄囊中发现具有统计学意义数量的CFU-S，并且尽管有一组报告称卵黄囊可重新填充W突变小鼠的造血系统，但其他研究人员未能证实卵黄囊可使成年动物重新造血。在鸟类和两栖类系统中，卵黄囊仅产生早期的、短暂的造血，而这些脊椎动物中确定的成年造血干细胞则源自包含背主动脉的中胚层区域。由于此前尚未对小鼠胚胎的这一类似区域进行造血活性检测，我们在胚胎发生过程中直接比较了主动脉、性腺、中肾（AGM）区域与卵黄囊和胎儿肝脏的CFU-S活性。在此我们报告，胚胎内的AGM区域所含CFU-S活性的频率高于胚胎卵黄囊，且这种活性在胎儿肝脏之前就出现在AGM区域。
