Self Renewal and Differentiation of Embryonic Stem Cells

描述（由申请人提供）：本申请名为“人类胚胎干细胞的自我更新和分化”，由我们的人类ES细胞核心实验室和四个项目组成。我们建议大幅扩大我们目前资助期间开始的工作，作为华盛顿大学/弗雷德哈钦森癌症研究中心（UW/FHCRC）“人类胚胎干细胞研究探索中心”。“我们的人类胚胎干细胞（hESC）核心实验室，由Carol Ware指导，已经获得并鉴定了21个NIH批准的人类ESC系中的14个，并协助18个实验室进行与hESC相关的工作。核心将收购其余NIH批准的hESC细胞系，将表征所有细胞系的microRNA表达谱，协助所有组成项目，并将继续协助使hESC可供当地80多个与hESC相关的实验室使用。由Blau和Ware博士领导的项目1将研究由短链脂肪酸丁酸盐激活的自我更新的替代途径。由Randall Moon领导的项目2将研究hESC中的经典和非经典Wnt信号通路。由Charles Murry领导的项目3检查了hESC在分化过程中向心肌细胞命运的方向发展，而由Tom Reh领导的项目4评估了向神经视网膜命运的定向分化。每个项目之间的逻辑和广泛的互动，以及hESC核心实验室，每个项目和UW/FHCRC其他实验室之间的广泛互动，创造了一个比其部分总和更强大的计划。

DESCRIPTION (provided by applicant): This application, entitled "Self Renewal and Differentiation of Human Embryonic Stem Cells," is comprised of our Human ES Cell Core Laboratory and four projects. We propose to dramatically expand the work begun during our current funding as a University of Washington/Fred Hutchinson Cancer Research Center (UW/FHCRC) "Exploratory Center for Human Embryonic Stem Ceil Research." Our Human ES Cell (hESC) Core Lab, directed by Carol Ware, has acquired and characterized 14 of the 21 NIH approved human ESC lines, and has assisted 18 laboratories in work related to hESCs. The Core will acquire the remaining NIH approved hESC lines, will characterize microRNA expression profiles of all lines, assist all of the component projects, and will also continue to assist in making hESCs accessible to a local community of more than 80 labs with interests relevant to hESCs. Project 1, led by Drs. Blau and Ware, will examine an alternative pathway for self-renewal that is activated by the short chain fatty acid, butyrate. Project 2, led by Randall Moon, will examine canonical and non-canonical Wnt signaling pathways in hESCs. Project 3, headed by Charles Murry, examines hESCs during differentiation directed toward a cardiomyocyte fate while Project 4, led by Tom Reh, evaluates directed differentiation toward a neuroretinal fate. Logical and extensive interactions between each of the projects, and extensive interactions between the hESC Core Lab, each of the projects, and other labs at UW/FHCRC create a Program vastly stronger than the sum of its parts.