Yoder M C, Hiatt K
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis 46202, USA.
Blood. 1997 Mar 15;89(6):2176-83.
Yolk sac hematopoiesis is characterized by restricted hematopoietic cell differentiation. Although multipotent hematopoietic progenitor cells have been identified in the early yolk sac, long-term multilineage repopulating (LTMR) hematopoietic stem cell (HSC) activity has not been demonstrable before day 11 postcoitus (PC) using standard transplantation assays. In the present study, day-10 PC yolk sac hematopoietic cells were infused into myeloablated congenic newborn pups and donor cell engraftment and multilineage reconstitution of peripheral blood cells for at least 11 months in primary recipients was observed. In contrast, transplantation of day-10 PC yolk sac cells into congenic adult recipients did not result in engraftment despite pretransplant conditioning of the recipients or use of recipients that were genetically deficient in stem cells. Although fresh yolk sac cells were incapable of reconstitution when injected into adult recipient mice, yolk sac donor-derived cells residing in the bone marrow of primary newborn transplant recipients were capable of efficient reconstitution of conditioned secondary recipient adult mice. Primary newborn and secondary adult recipient animals engrafted with yolk sac cells were observed to have normal peripheral blood white blood cell counts. Lymphocyte subsets in peripheral blood, thymus, and spleen were also similar to control animals. The distribution and frequency of lineage-restricted progenitors derived from bone marrow of secondary transplant recipients were normal. These results indicate that day-10 PC yolk sac HSCs are capable of engrafting and reconstituting the hematopoietic system of conditioned newborn but not adult recipient animals. Furthermore, the ability of the yolk sac HSCs to differentiate into all hematopoietic lineages in these recipients strongly suggests that the local cellular microenvironment plays a prominent role in regulating yolk sac HSC differentiation.
卵黄囊造血的特点是造血细胞分化受限。尽管在早期卵黄囊中已鉴定出多能造血祖细胞，但在交配后第11天（PC）之前，使用标准移植试验尚未证明存在长期多谱系重建（LTMR）造血干细胞（HSC）活性。在本研究中，将交配后第10天的PC卵黄囊造血细胞注入经清髓的同基因新生幼崽体内，并观察到初级受体中供体细胞植入以及外周血细胞的多谱系重建至少持续11个月。相比之下，尽管对受体进行了移植前预处理或使用了干细胞基因缺陷的受体，但将交配后第10天的PC卵黄囊细胞移植到同基因成年受体中并未导致植入。尽管将新鲜的卵黄囊细胞注入成年受体小鼠时无法实现重建，但存在于初级新生移植受体骨髓中的卵黄囊供体来源细胞能够有效地重建经预处理的次级受体成年小鼠。观察到植入卵黄囊细胞的初级新生和次级成年受体动物外周血白细胞计数正常。外周血、胸腺和脾脏中的淋巴细胞亚群也与对照动物相似。来自次级移植受体骨髓的谱系受限祖细胞的分布和频率正常。这些结果表明，交配后第10天的PC卵黄囊HSC能够植入并重建经预处理的新生受体而非成年受体动物的造血系统。此外，卵黄囊HSC在这些受体中分化为所有造血谱系的能力强烈表明，局部细胞微环境在调节卵黄囊HSC分化中起重要作用。
