Ody C, Vaigot P, Quéré P, Imhof B A, Corbel C
Département de Pathologie, Centre Médical Universitaire (CMU), Geneva, Switzerland.
Blood. 1999 May 1;93(9):2898-906.
The fibrinogen receptor GPIIb-IIIa integrin is known to be expressed on cells of the megakaryocytic lineage, but its presence on hematopoietic progenitors has been a controversial issue. To resolve this ambiguity unequivocally, we performed clonogenic assays and intrathymic cell-transfer experiments in congenic animals. As the ontogeny of the avian hematopoietic system is well documented, we used this experimental model to trace GPIIb-IIIa expression during embryogenesis. Consequently, we now report that the GPIIb-IIIa integrin is expressed as early as embryonic day 3.5 (E3.5) to 4 in intraaortic hematopoietic clusters, the first site of intraembryonic hematopoietic progenitor emergence, and later in E6 paraaortic foci. Myeloid and erythroid progenitors were also detected within the GPIIb-IIIa+ CD45(+) population isolated from the E3.5 to 4 aortic area, while in embryonic and adult bone marrow, myeloid, erythroid, and T-cell progenitors were present in the GPIIb-IIIa+ c-kit+ population. Furthermore, we also provide the first evidence, that GPIIb-IIIa+ bone marrow cells can differentiate into T cells. Hence, GPIIb-IIIa can be used as a marker for multilineage hematopoietic progenitors, permitting identification of early intraembryonic sites of hematopoiesis, as well as the isolation of embryonic and adult hematopoietic progenitors.
已知纤维蛋白原受体糖蛋白IIb-IIIa整合素在巨核细胞系细胞上表达,但其在造血祖细胞上的存在一直是个有争议的问题。为了明确解决这一模糊性,我们在同基因动物中进行了克隆形成试验和胸腺内细胞移植实验。由于鸟类造血系统的个体发生有充分记录,我们利用这个实验模型来追踪胚胎发育过程中糖蛋白IIb-IIIa的表达。因此,我们现在报告,糖蛋白IIb-IIIa整合素早在胚胎第3.5天(E3.5)至第4天就在主动脉内造血簇中表达,这是胚胎内造血祖细胞出现的第一个部位,随后在E6主动脉旁灶中表达。从E3.5至4主动脉区域分离的糖蛋白IIb-IIIa+ CD45(+)群体中也检测到了髓系和红系祖细胞,而在胚胎和成年骨髓中,髓系、红系和T细胞祖细胞存在于糖蛋白IIb-IIIa+ c-kit+群体中。此外,我们还提供了首个证据,即糖蛋白IIb-IIIa+骨髓细胞可以分化为T细胞。因此,糖蛋白IIb-IIIa可作为多谱系造血祖细胞的标志物,用于识别胚胎内早期造血部位,以及分离胚胎和成年造血祖细胞。