Transcriptional Regulation of Endothelial Differentiation by ERG

ERG 对内皮分化的转录调控

• 批准号: 8511780
• 负责人: Peter I Oettgen
• 金额: $ 41.42万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 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/8511780
• 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; paracrine; postnatal; progenitor; promoter; repaired; small hairpin RNA; stem cell differentiation; tissue processing; transcription factor; vasculogenesis

PROJECT SUMMARY (See instructions): ERG Is a member of the ETS transcription factor family that has recently been shown to participate in the regulation 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 tissues. Second, during embryonic stem (ES) cell differentiation, 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, downregulation of ERG in ES cells markedly inhibits EC differentiation 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 epigenetic regulation of endothelial differentiation by ERG The hypothesis for this aim is that ERG functions at multiple levels to regulate EC differentiation. ERG may act alone or in combination with other transcription factors to regulate EC-specific target genes such as VE-cadherin. Aim III will examine the role of ERG in regulating 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.

项目概述（见说明书）：ERG是ETS转录因子家族的一员，最近已被证明参与一些内皮限制性基因的调控，包括vWF、endoglin和VE-cadherin。我们的初步研究显示了ERG的几个独特特征。首先，ERG在整个血管发育过程和几个成人组织中表现出高度内皮细胞（EC）限制性表达模式。其次，在胚胎干细胞分化过程中，ERG首先在VEGF-R2+细胞亚群中表达，这些细胞也表达VE-cadherin。第三，ERG与沿内皮谱系分化的干细胞密切相关。第四，下调ES细胞ERG可显著抑制胚状体EC分化和血管结构形成。该建议的总体假设是ERG是EC分化和血管发育的关键转录调节因子。目的我将定义ERG在血管发育中的作用。在血管发育的早期阶段，ERG在几个组织和器官中以ec限制性模式表达。这一目的的假设是，ERG表达是血管发育所必需的。目的II将定义ERG对内皮细胞分化的转录和表观遗传调控，该目的的假设是ERG在多个水平上调节EC分化。ERG可单独或与其他转录因子联合作用，调控ec特异性靶基因，如ve -钙粘蛋白。目的III将研究ERG在调节内皮祖细胞功能和出生后血管生成中的作用内皮祖细胞（Endothelial progenitor cells， 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功能和产后血管发生的关键转录调节因子。