Huber Tara L, Kouskoff Valerie, Fehling H Joerg, Palis James, Keller Gordon
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York City, New York 10029, USA.
Nature. 2004 Dec 2;432(7017):625-30. doi: 10.1038/nature03122.
Haematopoietic and vascular cells are thought to arise from a common progenitor called the haemangioblast. Support for this concept has been provided by embryonic stem (ES) cell differentiation studies that identified the blast colony-forming cell (BL-CFC), a progenitor with both haematopoietic and vascular potential. Using conditions that support the growth of BL-CFCs, we identify comparable progenitors that can form blast cell colonies (displaying haematopoietic and vascular potential) in gastrulating mouse embryos. Cell mixing and limiting dilution analyses provide evidence that these colonies are clonal, indicating that they develop from a progenitor with haemangioblast potential. Embryo-derived haemangioblasts are first detected at the mid-streak stage of gastrulation and peak in number during the neural plate stage. Analysis of embryos carrying complementary DNA of the green fluorescent protein targeted to the brachyury locus demonstrates that the haemangioblast is a subpopulation of mesoderm that co-expresses brachyury (also known as T) and Flk-1 (also known as Kdr). Detailed mapping studies reveal that haemangioblasts are found at highest frequency in the posterior region of the primitive streak, indicating that initial stages of haematopoietic and vascular commitment occur before blood island development in the yolk sac.
造血细胞和血管细胞被认为起源于一种称为成血管细胞的共同祖细胞。胚胎干细胞（ES）分化研究为这一概念提供了支持，该研究鉴定出了胚细胞集落形成细胞（BL-CFC），这是一种具有造血和血管潜能的祖细胞。利用支持BL-CFC生长的条件，我们在原肠胚形成期的小鼠胚胎中鉴定出了可形成胚细胞集落（显示造血和血管潜能）的类似祖细胞。细胞混合和有限稀释分析提供了证据，表明这些集落是克隆性的，这表明它们是由具有成血管细胞潜能的祖细胞发育而来的。胚胎来源的成血管细胞最早在原肠胚形成的中胚层期被检测到，在神经板期数量达到峰值。对携带靶向短尾基因座的绿色荧光蛋白互补DNA的胚胎进行分析表明，成血管细胞是中胚层的一个亚群，它同时表达短尾蛋白（也称为T）和Flk-1（也称为Kdr）。详细的定位研究表明，成血管细胞在原条后部区域的出现频率最高，这表明造血和血管定向分化的初始阶段发生在卵黄囊中血岛发育之前。
