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Transcriptional Regulation of Endothelial Differentiation by ERG

ERG 对内皮分化的转录调控

基本信息

批准号：
8379165
负责人：
Peter I Oettgen
金额：
$ 43.5万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8379165
关键词：
Adult Affect Binding Binding Sites Biology Blood Vessels Boston Cell Differentiation process Cell Lineage Cell Separation Cell physiology Cells Collaborations Coronary Dependency Development Developmental Process Disease Down-Regulation EMSA Embryo Endoglin Endothelial Cells Epigenetic Process Exhibits Family Flow Cytometry Functional RNA Gene Cluster Gene Expression Gene Targeting Genes Goals Health Hematopoiesis Human Instruction Ischemia Knockout Mice Laboratories Lead Light Limb structure Link Maps Messenger RNA Molecular Mus Myocardial Myocardial Ischemia Organ Pathologic Patients Pattern Pediatric Hospitals Peripheral Vascular Diseases Phenotype Play Process Program Research Project Grants Regulation Regulatory Pathway Relative (related person)Reverse Transcriptase Polymerase Chain Reaction Role Site Staging Stem cells Structure TNF gene Tetracyclines Therapeutic Time Tissues Transcriptional Regulation Umbilical Cord Blood Untranslated RNA VWF gene Vascular Endothelial Growth Factors angiogenesis autocrine base cadherin 5 cell type embryonic stem cell fascinate gain of function in vivo insight interest knock-down member migration novel therapeutic intervention overexpression paracrine postnatal progenitor promoter repaired small hairpin RNA stem cell differentiation tissue processing transcription factor vasculogenesis

项目摘要

PROJECT SUMMARY (See instructions): ERG Is a member of the ETS transcription factor family that has recently been shown to participate in the regulafion of selected endothelial-restricted genes including vWF, endoglin, and VE-cadherin. Our preliminary studies demonstrate several unique features of ERG. First, ERG exhibits a highly endothelial cell (EC)-restricted expression pattern throughout vascular development and in several adult fissues. Second, during embryonic stem (ES) cell differenfiafion, ERG is first expressed in a subset of VEGF-R2+ cells that also express VE-cadherin. Third, ERG closely tracks with stem cells that differentiate along the endothelial lineage. Fourth, downregulafion of ERG in ES cells markedly inhibits EC differenfiafion and vascular structure formation in embryoid bodies (EB). The overall hypothesis for this proposal is that ERG is a critical transcriptional regulator of EC differentiation and vascular development. Aim I will define the role of ERG during vascular development. ERG is expressed in an EC-restricted pattern within several tissues and organs during early stages of vascular development. The hypothesis for this aim is that ERG expression is required for vascular development. Aim II will define the transcriptional and epigenefic regulafion of endothelial differenfiafion by ERG The hypothesis for this aim is that ERG funcfions at mulfiple levels to regulate EC differentiation. ERG may act alone or in combinafion with other transcription factors to regulate EC-specific target genes such as VE-cadherin. Aim III will examine the role of ERG in regulafing EPC function and postnatal vasculogenesis Endothelial progenitor cells (EPC) represent an important cell type that can promote vascular repair, angiogenesis and post-natal vasculogenesis. The hypothesis for this aim is that ERG is a critical transcriptional regulator of EPC function and post-natal vasculogenesis.

项目总结（见说明）： ERG是ETS转录因子家族的一员，最近被证明参与了调节选定的内皮限制性基因，包括vWF、内皮糖蛋白和VE-钙粘蛋白。我们初步研究表明ERG的几个独特特征。首先，ERG表现出高度内皮化的细胞（EC）-限制性表达模式在整个血管发育和几个成年裂殖体中。第二、在胚胎干（ES）细胞分化过程中，ERG首先在VEGF-R2+细胞亚群中表达，也表达VE-钙粘蛋白。第三，ERG与干细胞密切相关，干细胞沿着内皮细胞沿着分化，脉第四，ES细胞ERG的下调显著抑制EC分化和血管生成。胚状体（EB）结构形成。这一提议的总体假设是，ERG是一种 EC分化和血管发育的关键转录调节因子。目的我将定义的作用视网膜电图在血管发育中的作用ERG在几种组织中以EC限制模式表达，器官在血管发育的早期阶段。这一目标的假设是，ERG表达是是血管发育所必需的目的II将定义转录和表观遗传调控，视网膜电图对内皮细胞分化的作用这一目的的假设是，视网膜电图在多个水平发挥作用，调节EC分化。ERG可以单独或与其他转录因子联合作用， EC特异性靶基因，如VE-钙粘蛋白。目的III将研究ERG在调节EPC中的作用内皮祖细胞（EPC）是一种重要的细胞类型，可以促进血管修复、血管生成和出生后血管生成。这一目标的假设是 ERG是EPC功能和出生后血管发生的关键转录调节因子。