Endothelial Cell Role in Yolk Sac Stem Cell Development

内皮细胞在卵黄囊干细胞发育中的作用

• 批准号: 6990128
• 负责人: Mervin C. YODER
• 金额: $ 1.42万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6990128
• 关键词: Endothelial; Cell; Role; Yolk; Sac

DESCRIPTION (provided by applicant): The overall goal of our work is to elucidate the roles and molecular basis of endothelial and hematopoietic cell interactions in the establishment of the hematopoietic system in the mouse. Examination of the mechanisms of yolk sac blood island organogenesis is important to understand how the first organ in the mouse is formed and as a model to investigate how the hematopoietic and endothelial lineages arise from a common precursor. However, reagents to identify the earliest events in yolk sac hematopoiesis have been lacking. We present novel preliminary data that CD41 expression marks the onset of primitive and definitive hematopoiesis in the murine embryo. We have utilized confocal microscopy to identify the site of emergence of the progenitor cells of both primitive and definitive progenitors. We have also developed a strategy that permits isolation of pure populations of endothelial cells from embryonic or adult mouse organs. We now propose to address the following areas where significant information gaps exist in our field: 1. The mechanisms of yolk sac blood island development remain undefined. We hypothesize that blood cell formation occurs concomitant with vasculogenesis but that primitive erythroblast progenitor cells are formed outside of any endothelial lined lumen. We further hypothesize that definitive hematopoietic progenitor cells emerge as clusters of cells from the endothelial lining of the blood islands. Thus, primitive and definitive progenitors arise via different mechanisms, raising the question of whether they share a common precursor. 2. Direct evidence of hematopoietic progenitor cell seeding of the liver is lacking. We hypothesize that the day 10 fetal liver is seeded with circulating yolk sac CD41bright definitive progenitor cells in vivo and that yolk sac CD41 bright progenitor cells will preferentially adhere to fetal liver-derived endothelial cells in vitro. 3. Cells from vascular grafts protect mice from radiation-induced death but do not possess hematopoietic stem cell activity (HSC). We present preliminary evidence that yolk sac endothelial cells preferentially maintain HSC repopulating ability ex vivo compared to adult kidney or liver endothelial cells. We hypothesize that yolk sac and embryo proper endothelial cells will facilitate HSC engraftment upon transplantation in vivo

描述（由申请人提供）：我们工作的总体目标是阐明内皮细胞和造血细胞相互作用在小鼠造血系统建立中的作用和分子基础。检查卵黄囊血岛器官发生机制对于了解小鼠第一个器官是如何形成的以及作为研究造血和内皮谱系如何从共同前体产生的模型非常重要。然而，一直缺乏鉴定卵黄囊造血最早事件的试剂。我们提供了新的初步数据，表明 CD41 表达标志着小鼠胚胎中原始和确定造血作用的开始。我们利用共聚焦显微镜来识别原始祖细胞和定形祖细胞的祖细胞出现的位点。我们还开发了一种策略，允许从胚胎或成年小鼠器官中分离纯的内皮细胞群。我们现在建议解决我们领域中存在重大信息差距的以下领域： 1. 卵黄囊血岛发育的机制仍不清楚。我们假设血细胞形成与血管发生同时发生，但原始成红细胞祖细胞是在任何内皮衬里管腔之外形成的。我们进一步假设，确定的造血祖细胞作为来自血岛内皮衬里的细胞簇出现。因此，原始祖细胞和最终祖细胞通过不同的机制产生，这就提出了它们是否具有共同前体的问题。 2.缺乏肝脏造血祖细胞播种的直接证据。我们假设第 10 天的胎儿肝脏在体内接种了循环卵黄囊 CD41bright 定形祖细胞，并且卵黄囊 CD41bright 祖细胞将在体外优先粘附到胎儿肝脏来源的内皮细胞。 3. 来自血管移植物的细胞可以保护小鼠免受辐射引起的死亡，但不具有造血干细胞活性（HSC）。我们提出的初步证据表明，与成人肾或肝内皮细胞相比，卵黄囊内皮细胞优先维持 HSC 离体再增殖能力。我们假设卵黄囊和胚胎固有内皮细胞将促进体内移植后 HSC 的植入