Discordant developmental waves of angioblasts and hemangioblasts in the early gastrulating mouse embryo
Discordant developmental waves of angioblasts and hemangioblasts in the early gastrulating mouse embryo
复制标题
DOI：
10.1242/dev.02440
复制
发表时间：
2006-07-15
期刊：
影响因子：
4.6
通讯作者：
Nakauchi, Hiromitsu
中科院分区：
文献类型：
--
作者：
Furuta, Chie;Ema, Hideo;Nakauchi, Hiromitsu
血管生成和造血被认为是在血管和血液中细胞的共同祖细胞--成血管细胞中产生的。这一计划受到挑战的动力学分析血管内皮细胞和造血祖细胞在早期原肠胚小鼠胚胎。OP-9与细胞因子组合的共培养系统允许检测内皮祖细胞以及基质依赖性造血祖细胞。早在胚胎日（E）5.50天就检测到了内皮祖细胞，此后它们的数量增加。在E6.75检测到基质依赖性造血祖细胞，据报道，该时间点成血管细胞出现。在E7.50时检测到培养物中的集落形成单位（CFU-c），最有可能是通过与微环境接触由基质依赖性造血祖细胞产生的，伴随着卵黄囊中原始造血的开始。有核红细胞的存在和胚胎型珠蛋白在源自基质依赖性造血祖细胞和CFU-c的红系集落中的表达支持这些祖细胞协调建立原始造血的观点。使用Oct3/4启动子驱动的GFP转基因小鼠，早期内皮祖细胞、基质依赖性造血祖细胞和CFU-c均显示表达Oct3/4转录因子。在Oct3/4阳性细胞中，内皮祖细胞和造血祖细胞均存在于CD31阳性部分中，在CD31阴性部分中留下内皮祖细胞的子集。这些数据表明，Oct3/4阳性中胚层产生CD 31阴性成血管细胞、CD 31阳性成血管细胞和CD 31阳性成血管细胞。我们提出了一个独特的发展途径，其中成血管细胞谱系直接从中胚层分化之前和独立的成血管细胞的发展。
Vasculogenesis and hematopoiesis are thought to arise in hemangioblasts, the common progenitors of cells in vessels and in blood. This scheme was challenged by kinetic analysis of vascular endothelial and hematopoietic progenitors in early gastrulating mouse embryos. The OP-9co-culture system with a combination of cytokines permitted the detection of endothelial progenitors, as well as stroma-dependent hematopoietic progenitors. Endothelial progenitors were detected as early as embryonic day (E) 5.50, after which time their numbers increased. Stroma-dependent hematopoietic progenitors were detected at E6.75, the time point when hemangioblasts reportedly emerge. Colony-forming units in culture (CFU-c), most likely generated from stroma-dependent hematopoietic progenitors via contact with the microenvironment, were detected at E7.50, concomitant with the onset of primitive hematopoiesis in the yolk sac. The presence of nucleated erythrocytes and the expression of an embryonic-type globin in erythroid colonies derived from stroma-dependent hematopoietic progenitors and from CFU-c support the notion that these progenitors coordinately establish primitive hematopoiesis. Using Oct3/4 promoter-driven GFP transgenic mice, early endothelial progenitors, stroma-dependent hematopoietic progenitors, and CFU-c were all shown to express the Oct3/4 transcription factor. Among Oct3/4-positive cells, both endothelial and hematopoietic progenitors were present in the CD31-positive fraction, leaving a subset of endothelial progenitors in the CD31-negative fraction. These data imply that Oct3/4-positive mesoderm gives rise to CD31-negative angioblasts, CD31-positive angiboblasts and CD31-positive hemangioblasts. We propose a distinct developmental pathway in which the angioblast lineage directly diverges from mesoderm prior to and independent of hemangioblast development.