Cheng Xin, Huber Tara L, Chen Vincent C, Gadue Paul, Keller Gordon M
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Development. 2008 Oct;135(20):3447-58. doi: 10.1242/dev.025916. Epub 2008 Sep 17.
During embryonic development, the establishment of the primitive erythroid lineage in the yolk sac is a temporally and spatially restricted program that defines the onset of hematopoiesis. In this report, we have used the embryonic stem cell differentiation system to investigate the regulation of primitive erythroid development at the level of the hemangioblast. We show that the combination of Wnt signaling with inhibition of the Notch pathway is required for the development of this lineage. Inhibition of Notch signaling at this stage appears to be mediated by the transient expression of Numb in the hemangioblast-derived blast cell colonies. Activation of the Notch pathway was found to inhibit primitive erythropoiesis efficiently through the upregulation of inhibitors of the Wnt pathway. Together, these findings demonstrate that specification of the primitive erythroid lineage is controlled, in part, by the coordinated interaction of the Wnt and Notch pathways, and position Numb as a key mediator of this process.
在胚胎发育过程中，卵黄囊中原始红细胞谱系的建立是一个在时间和空间上受到限制的程序，它定义了造血作用的起始。在本报告中，我们利用胚胎干细胞分化系统，在成血管细胞水平上研究原始红细胞发育的调控。我们发现，Wnt信号与Notch信号通路抑制的联合作用是该谱系发育所必需的。在此阶段，Notch信号通路的抑制似乎是由成血管细胞来源的胚细胞集落中Numb的瞬时表达介导的。研究发现，Notch信号通路的激活通过上调Wnt信号通路抑制剂而有效抑制原始红细胞生成。这些发现共同表明，原始红细胞谱系的特化部分受Wnt和Notch信号通路的协同相互作用控制，并将Numb定位为这一过程的关键介质。
