Self Renewal and Differentiation of Embryonic Stem Cells

描述(申请人提供)：这项名为“人类胚胎干细胞的自我更新和分化”的申请由我们的人类胚胎干细胞核心实验室和四个项目组成。我们建议极大地扩大我们目前资助的华盛顿大学/弗雷德·哈钦森癌症研究中心(UW/FHCRC)“人类胚胎干细胞细胞研究探索性中心”的工作。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NIH批准的21个人类胚胎干细胞系中的14个，并协助了18个实验室开展与人类胚胎干细胞相关的工作。CORE将收购NIH批准的其余hESCs品系，将表征所有品系的microRNA表达谱，协助所有组成部分项目，并将继续协助80多个与hESCs相关的当地社区获得hESCs。由Blau博士和Ware博士领导的项目1将研究一种由短链脂肪酸丁酸盐激活的自我更新的替代途径。由兰德尔·穆恩领导的项目2将研究人类胚胎干细胞中规范和非规范的Wnt信号通路。由Charles Murry领导的项目3检查分化过程中的hESCs，定向分化为心肌细胞的命运，而项目4，由Tom Reh领导，评估定向分化为神经视网膜的命运。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，创造了一个远远强于其各部分总和的计划。

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.