Control of Multineage Human ESC Differentiation

产品说明：（申请人提供）：人类胚胎干细胞（hESC）分化成所有细胞谱系的非凡潜力使其成为基础水平研究发育过程的有吸引力的候选者，也是再生医学中细胞或组织替代的候选者。因此，深入了解它们的确切潜力对于尽可能有效地推动这些领域的发展至关重要。这些细胞系似乎都能够分化为所有三个胚胎生殖细胞层的衍生物，然而，由于使用这些细胞的大量实验室中的不同培养条件，尚不清楚当评估在平行条件下的分化能力时，这些细胞系的行为究竟有多相似或不同。本项目的研究人员已经确定了几种联邦批准的人胚胎干细胞对相同分化诱导信号反应能力的实质性差异。这些信号被设计为使hESC向神经元、生殖细胞和造血谱系分化，因此我们看到这些细胞沿沿着多个谱系分化的显著差异 .该计划将通过行政核心（核心A）进行监督和协调，包含3个研究项目，旨在优化和表征联邦批准的4个hESC系沿着这三个谱系的分化，并评估与不同分化概况相关的潜在表观遗传变化。这三个项目将与干细胞核心（Core B）相互作用，后者将提供hESC，优化这些细胞作为未分化干细胞的培养，并开发用于hESC培养和分化的新型表面。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（核心D）相互作用，这将促进基因表达的表观遗传控制实验。每个项目将是独立的，但将相互交换数据，这样从未分化的hESC到所有三个谱系的分化的表观遗传谱将被组装。因此，我们将采用分化结果的持续比较和反馈来确定某些hESC系的表观遗传特征是否导致具有分化的一些或所有三个谱系的产量或质量提高。总之，我们将探索hESC分化潜能和沿沿着神经元、生殖细胞和造血谱系分化的表观遗传控制。

DESCRIPTION: (provided by applicant): 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.