Self Renewal and Differentiation of Human Embryonic Stem Cells

描述(由申请人提供)：本申请寻求对以人类多能干细胞研究为中心的高效合作的重新支持。该POI的调查人员代表了一个高度互动和协作的群体。每个项目都与至少两个其他项目和核心广泛互动。项目1(BLAU)将使用新的体内和体外模型剖析干细胞静止的分子基础。项目2(月球)将描述人类多能干细胞及其分化的中胚层和心肌细胞后代中Wnt信号的上下文相关变化(与项目3合作)。此外。项目2正在开发一组信号报告人类多能干细胞系，这些系将被证明对项目1、3和4在理解不同的多能状态和分化过程中的信号差异方面具有极其重要的价值。项目3(Murry)将测试他们在当前资金期间确定的心肌细胞分化的新候选调节器。项目4(REH)将与项目1和项目3有关处于静止和成熟状态的microRNAs的生物学。我们的核心是在项目工作的基本方面为其提供支持。我们的干细胞核心A(WARE)将与项目1、3和4合作，研究代谢物是否可以作为不同的多能性状态的驱动因素或直接分化，并将与项目3和4合作，以确定定位人类多能干细胞系以生成心肌细胞或神经视网膜细胞的方法。我们的计算生物学核心B(Ruzzo)将为每个项目以及核心A提供生物信息学支持，并将这些信息与现有的遗传和医学数据集整合在一起。这些项目和核心之间的广泛互动确保了从该计划项目中获得的总知识远远超过其各部分的总和。

DESCRIPTION (provided by applicant): This application seeks renewed support for a highly productive collaboration centered on human pluripotent stem cell research. The investigators of this POI represent a highly interactive and collaborative group. Each of the projects interacts extensively with at least two of the other Projects and Cores. Project 1 (Blau) will dissect the molecular basis of stem cell quiescence using novel in vivo and in vitro models. Project 2 (Moon) will characterize context dependent changes in Wnt signaling in human pluripotent stem cells and their differentiated mesodermal and cardiomyocyte progeny (in collaboration with Project 3). In addition. Project 2 is developing a panel of signaling reporter human pluripotent stem cell lines and these lines will prove extremely valuable to Projects 1, 3 and 4 in understanding how signaling differs between distinct pluripotent states and during differentiation. Project 3 (Murry) will test novel candidate regulators of cardiomyocyte differentiation that they identified during the current funding period. Project 4 (Reh) will interat with Projects 1 and 3 on the biology of microRNAs in quiescence and maturation. Our Cores are designed to support the projects in essential aspects of their work. Our Stem Cell Core A (Ware) will work with Projects 1, 3 and 4 to examine whether metabolites can act as drivers of distinct states of pluripotency or to direct differentiation, and will work with Projects 3 and 4 to identif methods for positioning human pluripotent stem cell lines to generate cardiomyocytes or neuroretinal cells. Our Computational Biology Core B (Ruzzo) will provide bioinformatics support for each of the projects as well as for Core A, and will integrate this information with existing genetic and medical datasets. These extensive interactions between the Projects and the Cores assure that the aggregate knowledge to be gained from this Program Project vastly exceeds the sum of its parts.