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: 7391197
• 负责人: Mervin C. YODER
• 金额: $ 40.15万
• 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/7391197
• 关键词: Accounting; Address; Angioblast; Biological Assay; Blood; Blood Cells; Blood Island; Blood Vessels; Blood capillaries; Cell Aggregation; Cells; Chick Embryo; Confocal Microscopy; Data; Development; Differentiation and Growth; Distal; Embryo; Endoderm; Endothelial Cells; Erythroblasts; Erythroid; Erythroid Progenitor Cells; Event; Extracellular Matrix; Fibronectins; Flow Cytometry; Glean; Goals; Growth Factor; Hematopoiesis; Hematopoietic; Hematopoietic stem cells; Image; Image Analysis; Immigration; In Situ; In Vitro; Integrins; Maps; Mediating; Mesoderm; Molecular; Mus; Mutant Strains Mice; Numbers; Organogenesis; Pathway interactions; Peptides; Platelet Glycoproteins; Population; Process; Production; Reagent; Recruitment Activity; Role; Signal Transduction; Site; Stem Cell Development; Stem cells; Sum; Testing; Vascular Endothelial Growth Factors; Visceral; Work; Yolk Sac; capillary; capillary bed; day; embryo culture; embryonic stem cell; innovation; insight; migration; novel; progenitor; prospective; response

The overall goal of our work is to elucidate the molecular mechanisms of yolk sac blood island organogenesis. These studies will provide new insights into the relationship between blood and endothelial cell development in the first site of blood cell production. To date, 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 and have developed a strategy that permits isolation of primitive erythroid progenitor cells (EryP) from embryos or embryonic stem cell-derived embryoid bodies. We propose 3 aims to define the roles of specific molecules in the process of blood island organogenesis: 1. To determine the mechanism of EryP migration and expansion in the proximal yolk sac. We hypothesize that EryP migration and expansion in the proximal yolk sac are VEGF dependent. 2. To define the mechanism of angioblast and extracellular matrix fibronectin (Fn) interaction that results in blood island organogenesis. We hypothesize that blood island formation and remodeling into a capillary bed is a Fn dependent process whereby angioblasts migrate via integrin-Fn interactions to circumscribe the band of primitive erythroblasts in the proximal yolk sac to form intact blood islands. 3. To determine the mechanism of CD41 bright cell cluster formation. We hypothesize that CD41 bright cell clusters require the expression of Runxl and GATA2 for emergence from the endothelial cells located between blood islands and pre-established capillaries (devoid of blood cells) in the distal yolk sac. These studies will define molecular pathways required for blood island development and remodeling.

我们工作的总体目标是阐明卵黄囊血岛器官发生的分子机制。这些研究将为血液和内皮细胞发育之间的关系提供新的见解，这些内皮细胞发育是血细胞产生的第一个部位。到目前为止，试剂，以确定卵黄囊造血的最早期事件一直缺乏。我们目前的新的初步数据表明，CD41的表达标志着在小鼠胚胎的原始和永久造血的发病。我们已经利用共聚焦显微镜，以确定原始和永久祖细胞的祖细胞出现的网站，并已开发出一种策略，允许分离的原始红系祖细胞（EryP）从胚胎或胚胎干细胞衍生的胚状体。我们提出3个目标来确定特定分子在血岛器官形成过程中的作用：1。探讨EryP在近端卵黄囊中迁移和扩张的机制。我们推测EryP在近端卵黄囊的迁移和扩张是VEGF依赖性的。2.目的探讨成血管细胞与细胞外基质纤维连接蛋白（Fn）相互作用导致血岛器官形成的机制。我们假设血岛的形成和重塑成毛细血管床是一个Fn依赖的过程，其中成血管细胞迁移通过整合素Fn相互作用，以限制带的原始成红细胞在近端卵黄囊，形成完整的血岛。3.探讨CD41亮细胞簇形成的机制。我们假设CD41亮细胞簇需要Runxl和GATA 2的表达，以从位于远端卵黄囊中的血岛和预先建立的毛细血管（缺乏血细胞）之间的内皮细胞中出现。这些研究将确定血岛发育和重塑所需的分子途径。

项目成果

The multiple facets of hematopoietic stem cells.

造血干细胞的多个方面。

• DOI: 10.2174/1567202043362324
• 发表时间: 2004
• 期刊: Current neurovascular research
• 影响因子: 2.1
• 作者: Chan,RebeccaJ;Yoder,MervinC
• 通讯作者: Yoder,MervinC

VEGF and IHH rescue definitive hematopoiesis in Gata-4 and Gata-6-deficient murine embryoid bodies.

• DOI: 10.1016/j.exphem.2009.05.011
• 发表时间: 2009-09
• 期刊: EXPERIMENTAL HEMATOLOGY
• 影响因子: 2.6
• 作者: Pierre, Monique;Yoshimoto, Momoko;Huang, Lan;Richardson, Matthew;Yoder, Mervin C.
• 通讯作者: Yoder, Mervin C.

Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level.

• DOI: 10.1038/ncomms3924
• 发表时间: 2013
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Swiers, Gemma;Baumann, Claudia;O'Rourke, John;Giannoulatou, Eleni;Taylor, Stephen;Joshi, Anagha;Moignard, Victoria;Pina, Cristina;Bee, Thomas;Kokkaliaris, Konstantinos D.;Yoshimoto, Momoko;Yoder, Mervin C.;Frampton, Jon;Schroeder, Timm;Enver, Tariq;Goettgens, Berthold;de Bruijn, Marella F. T. R.
• 通讯作者: de Bruijn, Marella F. T. R.

Evaluation of primitive murine hematopoietic stem and progenitor cell transduction in vitro and in vivo by recombinant adeno-associated virus vector serotypes 1 through 5.

重组腺相关病毒载体血清型 1 至 5 对原始小鼠造血干细胞和祖细胞转导的体外和体内评价。

• DOI: 10.1089/hum.2006.17.321
• 发表时间: 2006
• 期刊: Human gene therapy
• 影响因子: 4.2
• 作者: Zhong,Li;Li,Weiming;Li,Yanjun;Zhao,Weihong;Wu,Jianqing;Li,Baozheng;Maina,Njeri;Bischof,Daniela;Qing,Keyun;Weigel-Kelley,KirstenA;Zolotukhin,Irene;WarringtonJr,KennethH;Li,Xiaomiao;Slayton,WilliamB;Yoder,MervinC;Srivastav
• 通讯作者: Srivastav

Effect of developmental stage of HSC and recipient on transplant outcomes.

• DOI: 10.1016/j.devcel.2014.04.013
• 发表时间: 2014-06-09
• 期刊: DEVELOPMENTAL CELL
• 影响因子: 11.8
• 作者: Arora, Natasha;Wenzel, Pamela L.;McKinney-Freeman, Shannon L.;Ross, Samantha J.;Kim, Peter G.;Chou, Stephanie S.;Yoshimoto, Momoko;Yoder, Mervin C.;Daley, George Q.
• 通讯作者: Daley, George Q.