Cardiac Differentiation from Human Embryonic Stem Cells

人胚胎干细胞向心脏分化

• 批准号: 7903426
• 负责人: Charles E Murry
• 金额: $ 33.58万
• 依托单位: UNIVERSITY OF WASHINGTON
• 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/7903426
• 关键词: Activins; Area; BMP4; Basic Science; Butyrates; Cardiac; Cardiac Myocytes; Cell Death; Cell Proliferation; Cells; Cellular biology; Classification; Collaborations; Commit; Ectoderm; Gastrula; Goals; Heart; Heart Atrium; Human; Human Development; Immune; Laboratories; Mesoderm; MicroRNAs; Molecular; Moon; Mus; Muscle Cells; Myocardium; Natural regeneration; Pathway interactions; Play; Population; Research; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Role; Signal Pathway; Signal Transduction; Specificity; Staging; System; Testing; Time; Transcriptional Regulation; Treatment Protocols; Ventricular; Western Blotting; Work; Wound Healing; Zebrafish; activin A; bone morphogenetic protein 4; cardiogenesis; embryonic stem cell; human embryonic stem cell; overexpression; progenitor; programs; receptor; research study; retinal progenitor cell; self-renewal

Project 3. Cardiac Differentiation from Human Embryonic Stem Cells (Charles E. Murry, Project Leader) The long term goals of this work are to understand pathways controlling differentiation of cardiomyocytes from human embryonic stem cells (hESCs). These pluripotent cells offer a system for basic research in human development and cell biology, as well as potential applications for tissue repair and regeneration. Traditional ESC differentiation systems, such as embryoid bodies, are heterogeneous and yield cardiomyocytes at low efficiency, typically <1%. This lack of purity and low yield has significantly impeded research. In collaboration with colleagues at Geron, we recently developed a system for directed differentiation of hESCs, using Activin A and BMP4, which yields -50% cardiomyocytes before purification and >95% myocytes after purification. Furthermore, in collaboration with Dr. Moon's laboratory (Project 2), we have shown a potent role for Wnt/b-catenin signaling in control of cardiogenesis in mouse ESCs. The ability to efficiently control ESC differentiation makes possible systematic studies into the mechanism of human cardiac differentiation and could yield populations of cells, such as pre-cardiac mesodermal progenitors, that have remained elusive due to technical limitations. The current proposal therefore focuses on optimizing these regimens and understanding key molecular and cellular steps in cardiac differentiation from hESCs.

项目3。与人类胚胎干细胞的心脏分化（项目负责人Charles E. Murry） 这项工作的长期目标是了解控制心肌细胞差异的途径 来自人类胚胎干细胞（HESC）。这些多能单元为基础研究提供了 人类发育和细胞生物学以及组织修复和再生的潜在应用。 传统的ESC分化系统，例如胚胎体，是异质和产量的 低效率的心肌细胞通常<1％。这种缺乏纯度和低收率已极大地阻碍 研究。与Geron的同事合作，我们最近开发了一个用于指导的系统 使用激活素A和BMP4的hESC分化，在纯化前产生-50％的心肌细胞 纯化后> 95％的肌细胞。此外，与Moon博士的实验室合作（项目2）， 我们已经显示出Wnt/B-catenin信号在控制小鼠ESC中的心脏病中的有效作用。这 有效控制ESC差异化的能力使系统研究可能 人类心脏分化并可能产生细胞种群，例如心脏前中胚层 由于技术局限性，祖先仍然难以捉摸。因此，当前的提议重点 在优化这些方案并了解心脏分化的关键分子和细胞步骤 来自hESC。