DIFFERENTIATION OF MOUSE YOLK SAC ENDOTHELIAL CELLS

研究提出了分析的几个离散的步骤， 在哺乳动物发育过程中， 胚胎发育，产生不同的血管，包括 新生器官的微血管 这些步骤被认为是 包括：1）从假定的造血成血管细胞出现， 干细胞产生循环系统的各种谱系， 血液和生成血管的成血管细胞。 成血管细胞是 首先在胚外卵黄囊中检测到， 合并产生第一个可见的微血管。 虽然 随后初始血管可分支并穿过不同的血管 器官雏形（血管生成），大量的成血管细胞迁移 作为个体细胞发育成器官雏形， 特殊微血管床的形成（血管发生）。 什么 在很大程度上，还存在着对当地产生的 间充质细胞在不同器官微血管形成中的作用 地点不详。 为了研究事件的发展顺序， 微血管实验的目的是： 1. a. 鉴定和分离卵黄囊成血管细胞; B. 从细胞表面的角度来描述这些成血管细胞 表型，对生长因子的反应，特异性激酶的表达， 细胞因子的合成; C. 开发允许成血管细胞增殖的方法， 分化，从而建立成血管细胞系; D. 建立允许成血管细胞形成三维 试管或开放的血管。 2. a. 确定肺特异性属性的出现， 发育中的肺原基由卵黄囊成血管细胞（1a或1c; 血管生成）或被卵黄囊微血管穿透（1d;血管生成） B. 类似地确定心肌的分化模式 心脏发育中的相关微血管 C. 描绘大脑特定属性的外观， 前脑/大脑微血管的发育 3. 分析，使用上述生成的信息，最早出现 血管内皮细胞内细胞团细胞中成血管细胞特异性的特性， 早期胚胎或由胚胎干细胞（ES细胞）前体产生。 总之，这些研究将提供一个图片，如何器官特异性 哺乳动物胚胎中存在微脉管系统的异质性。 对这一过程的理解可能会导致制定战略， 选择性增强或抑制血管形成， 深入了解这种特殊的血管分化， 与炎症，肿瘤的建立，或广泛的发病机制 一系列血管生成性疾病。

Studies are proposed to analyze the several discrete steps by which the most primitive precursors of endothelial cells can, during mammalian embryonic development, generate the diverse blood vessels that comprise the microvasculature of the emerging organs. These steps are believed to include: 1) the emergence from postulated hemangioblasts of hematopoietic stem cells which give rise to tahe various lineages of the circulating blood, and angioblasts which give rise to blood vessels. Angioblasts are first detectable in the extraembryonic yolk sac where they can be shown to coalesce to give rise to the first visible microvessels. Although subsequently the initial blood vessels may branch and penetrate different organ rudiments (angiogenesis), a significant number of angioblasts migrate as individual cells into developing organ rudiments to participate there in the formation of specific microvascular beds (vasculogenesis). To what extent there is also differentiation and recruitment of locally arising mesenchymal cells in the formation of the microvessels in different organ sites is not known. To study the sequence of events underlying the development of the microvasculature experiments are proposed to: 1. a. Identify and isolate yolk sac angioblasts; b. Characterize these angioblasts in terms of their cell surface phenotype, response to growth factors, expression of specific kinases and synthesis of cytokines; c. Develop methods that permit angioblast proliferation without differentiation, thus establishing angioblast cell lines; d. Establish methods that permit angioblasts to form three-dimensional tubes or patent vessels in vitro. 2. a. determine the emergence of lung-specific properties in the developing lung rudiment seeded by yolk sac angioblasts (1a or 1c; vasculogenesis) or penetrated by yolk sac microvessels (1d; angiogenesis) b. similarly determine the pattern of differentiation of myocardium associated microvessels during heart development c. delineate the appearance of brain-specific properties in the developing microvasculature of the forebrain/cerebrum 3. analyze, using the information generated above, the earliest emergence of angioblast-specific properties in cells from the inner cell mass of the early embryo or generated from embryonic stem cell (ES cell) precursors. Together, these studies will provide a picture of how organ-specific heterogeneity of the microvasculature occurs in the mammalian embryo. Understanding of this process may lead to development of strategies for selective augmentation or inhibition of blood vessel formation and provide insight into such specialized vascular differentiations as those associated with inflammation, establishment of tumors, or the pathogenesis of a wide array of angiogenic diseases.