McEwen Centre for Regenerative Medicine, University Health Network, Toronto, ON, Canada.
Dev Cell. 2012 Jul 17;23(1):45-57. doi: 10.1016/j.devcel.2012.05.021. Epub 2012 Jun 28.
Primitive erythropoiesis defines the onset of hematopoiesis in the yolk sac of the early embryo and is initiated by the emergence of progenitors assayed as colony-forming cells (EryP-CFCs). EryP-CFCs are detected for only a narrow window during embryonic development, suggesting that both their initiation and termination are tightly controlled. Using the embryonic stem differentiation system to model primitive erythropoiesis, we found that miR-126 regulates the termination of EryP-CFC development. Analyses of miR-126 null embryos revealed that this miR also regulates EryP-CFCs in vivo. We identified vascular cell adhesion molecule-1 (Vcam-1) expressed by a mesenchymal cell population as a relevant target of miR-126. Interaction of EryP-CFCs with Vcam-1 accelerated their maturation to ßh1-globin(+) and Ter119(+) cells through a Src family kinase. These findings uncover a cell nonautonomous regulatory pathway for primitive erythropoiesis that may provide insight into the mechanism(s) controlling the developmental switch from primitive to definitive hematopoiesis.
原始红细胞生成定义了胚胎卵黄囊中造血的开始，是由集落形成细胞（EryP-CFC）测定的祖细胞出现引发的。EryP-CFC 仅在胚胎发育的一个狭窄窗口中被检测到，这表明其起始和终止都受到严格控制。我们使用胚胎干细胞分化系统来模拟原始红细胞生成，发现 miR-126 调节 EryP-CFC 发育的终止。对 miR-126 缺失胚胎的分析表明，该 miRNA 也在体内调节 EryP-CFC。我们确定了一种由间充质细胞群表达的血管细胞黏附分子-1（VCAM-1），作为 miR-126 的一个相关靶标。EryP-CFC 与 VCAM-1 的相互作用通过Src 家族激酶加速其向 ßh1-球蛋白（+）和 Ter119（+）细胞的成熟。这些发现揭示了原始红细胞生成的非细胞自主调节途径，这可能为控制从原始到定型造血的发育开关的机制提供了深入的了解。
