Control of Multineage Human ESC Differentiation

人类胚胎干细胞的巨大潜力 人胚胎干细胞（hESC）分化为所有细胞谱系使其成为研究发育的有吸引力的候选者 在基础水平上的过程，也作为候选人的细胞或组织替代再生 药因此，深入了解它们的确切潜力是推动这些领域发展的必要条件 尽可能高效地前进。这些线似乎都能够分化成所有 三个胚胎生殖细胞层，然而，由于不同的培养条件，在大量的 实验室使用这些细胞，目前还不清楚这些细胞系的行为究竟有多相似或不同 当评估在平行条件下的区分能力时。本计划项目中的研究人员 已经确定了几种联邦批准的hESC对以下疾病的反应能力的实质性差异： 相同的分化诱导信号。这些信号被设计为将hESC分化为 神经元，生殖细胞和造血谱系，因此，我们看到了分化的深刻差异， 这些细胞沿着多个谱系。该方案将通过以下机构进行监督和协调： 行政核心（核心A），包含3个研究项目，旨在优化和表征 沿着这三个谱系的4个联邦批准的hESC系的分化，并评估 与不同分化谱相关的潜在表观遗传变化。这三个项目将 与干细胞核心（核心B）相互作用，这将提供hESC，优化这些细胞的培养， 未分化的干细胞，并开发用于hESC培养和分化的新表面。这些 项目还将与表观遗传核心（核心C）和计算和生物信息学核心互动 (Core这将有助于基因表达的表观遗传控制实验。每个项目将 独立，但将彼此交换数据，使得来自 将组装通过向所有三个谱系分化的未分化hESC。我们将 采用差异化结果的持续比较和反馈，以确定 某些hESC系的表观遗传标记导致某些或所有三种细胞系的产量或质量提高。 有分化的谱系。总之，我们将探索hESC分化潜力， 沿着神经元、生殖细胞和造血谱系分化的表观遗传控制。

The extraordinary potential of human embryonic stem cells (hESC) to differentiate into all cell lineages makes them attractive candidates to study developmental processes at the basic level, and also as candidates for cell or tissue replacement in regenerative medicine. Thus an in-depth understanding of their exact potential is imperative to move these fields forward as efficiently as possible. These lines all appear to be able to differentiate into derivatives of all three embryonic germ cell layers, however due to different culture conditions in the large numbers of laboratories using these cells, it is unclear exactly how similarly or differently these lines will behave when assessed for ability to differentiate under parallel conditions. Investigators in this Program Project have identified substantial differences in the abilities of several federally approved hESC to respond to identical differentiation-inducing signals. These signals were designed to differentiate hESC towards neuronal, germ cell and hematopoietic lineages, thus we see profound differences in differentiation of these cells along multiple lineages. The Program will be overseen and coordinated through the Administrative Core (Core A) and contains 3 research projects designed to optimize and characterize the differentiation of 4 federally approved hESC lines along these three lineages, and to assess potential epigenetic changes associated with differing differentiation profiles. These three projects will interact with the Stem Cell Core (Core B), which will provide hESC, optimize culturing of these cells as non-differentiated stem cells, and develop novel surfaces for hESC culture and differentiation. These Projects will also interact with the Epigenetic Core (Core C) and Computational and Bioinformatics Core (Core D), which will facilitate experiments on epigenetic control of gene expression. Each project will be independent, but will exchange data with each other, such that an epigenetic profile from undifferentiated hESC through differentiation towards all three lineages will be assembled. Thus we will employ continual comparison and feedback of differentiation results to determine whether the epigenetic signature of certain hESC lines results in improved yield or quality of some or all three lineages with differentiation. Taken together we will explore hESC differentiation potential and epigenetic control of differentiation along neuronal, germ cell, and hematopoietic lineages.