Expression of CD41 marks the initiation of definitive hematopoiesis in the mouse embryo
Expression of CD41 marks the initiation of definitive hematopoiesis in the mouse embryo
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DOI：
10.1182/blood-2002-06-1699
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发表时间：
2003-01-15
期刊：
影响因子：
20.3
通讯作者：
Orkin, SH
中科院分区：
文献类型：
--
作者：
Mikkola, HKA;Fujiwara, Y;Orkin, SH
小鼠造血干细胞（HSC）起源于中胚层，其过程需要转录因子SCL/Tal 1。为了确定血细胞命运的承诺步骤，我们比较了野生型和SCL-/-胚胎干细胞体外分化，并将CD 41（GpIIb）鉴定为SCL-/-胚状体（EB）缺失的最早表面标志物。荧光激活细胞分选仪（FACS）纯化的EB细胞的培养显示，永久造血祖细胞高度富集在CD 41（+）部分，而内皮细胞从CD 41（-）细胞发展。在小鼠胚胎中，在卵黄囊血岛和胎肝中检测到CD 41的表达。在卵黄囊和EB中，泛造血标志物CD 45出现在CD 41+细胞亚群中。然而，多系造血集落不仅来自CD 45（+）CD 41（+）细胞，而且也来自CD 45（-）CD 41（+）细胞，这表明在胚胎阶段，CD 41而不是CD 45标志着定型培养集落形成单位（CFU-C）。相反，胎肝CFU-C为CD 45（+），只有一个亚部分表达CD 41，表明CD 41随胎肝分期下调。在卵黄囊和EB中，CD 41与胚胎HSC标记物c-kit和CD 34共表达。CD 41和c-kit表达的分选导致永久造血祖细胞的富集。此外，CD 41（+）c-kit（+）人群在缺乏明确造血的runx 1/AML 1（-/-）EB中缺失。这些结果表明，CD 41，SCL/Tal 1的候选靶基因，和c-kit的表达定义的分化，从内皮细胞发育过程中的最终造血。虽然CD 41通常被称为巨核细胞-血小板整合素在成人造血，这些结果暗示了更广泛的作用，CD 41在小鼠个体发育。(C)2003年，美国血液学会。
Murine hematopoietic stem cells (HSCs) originate from mesoderm in a process that requires the transcription factor SCL/Tal1. To define steps in the commitment to blood cell fate, we compared wild-type and SCL-/- embryonic stem cell differentiation in vitro and identified CD41 (GpIlb) as the earliest surface marker missing from SCL-/- embryoid bodies (EBs). Culture of fluorescence-activated cell sorter (FACS) purified cells from EBs showed that definitive hematopoietic progenitors were highly enriched in the CD41(+) fraction, whereas endothelial cells developed from CD41(-) cells. In the mouse embryo, expression of CD41 was detected in yolk sac blood islands and in fetal liver. In yolk sac and EBs, the panhematopoietic marker CD45 appeared in a subpopulation of CD41+ cells. However, multilineage hematopoietic colonies developed not only from CD45(+)CD41(+) cells but also from CD45(-)CD41(+) cells, suggesting that CD41 rather than CD45 marks the definitive culture colony-forming unit (CFU-C) at the embryonic stage. In contrast, fetal liver CFU-C was CD45(+), and only a sub-fraction expressed CD41, demonstrating down-regulation of CD41 by the fetal liver stage. In yolk sac and EBs, CD41 was coexpressed with embryonic HSC markers c-kit and CD34. Sorting for CD41 and c-kit expression resulted in enrichment of definitive hematopoietic progenitors. Furthermore, the CD41(+) c-kit(+) population was missing from runx1/AML1(-/-) EBs that lack definitive hematopoiesis. These results suggest that the expression of CD41, a candidate target gene of SCL/Tal1, and c-kit define the divergence of definitive hematopoiesis from endothelial cells during development. Although CD41 is commonly referred to as megakaryocyte-platelet integrin in adult hematopoiesis, these results implicate a wider role for CD41 during murine ontogeny. (C) 2003 by The American Society of Hematology.