Control of Multineage Human ESC Differentiation

描述：（由申请人提供）：人类胚胎干细胞（hESC）分化为所有细胞谱系的非凡潜力使其成为基础水平上研究发育过程的有吸引力的候选者，也成为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种胚胎生殖细胞层的衍生物，然而，由于在大量使用这些细胞的实验室中不同的培养条件，目前尚不清楚这些细胞系在平行条件下评估分化能力时的相似或不同表现。该项目的研究人员已经确定了几个联邦政府批准的hESC对相同分化诱导信号的反应能力存在实质性差异。这些信号被设计用于将hESC分化为神经元、生殖细胞和造血细胞谱系，因此我们看到这些细胞沿着多个谱系分化的深刻差异。该计划将通过行政核心（Core A）进行监督和协调，包括3个研究项目，旨在优化和表征这三个谱系中4个联邦批准的hESC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培养和分化的新表面。这些项目还将与表观遗传核心（Core C）和计算与生物信息学核心（Core 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到分化到所有三个谱系的表观遗传谱将被组装起来。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会导致部分或全部三个分化谱系的产量或质量提高。总之，我们将探索沿神经元、生殖细胞和造血谱系的hESC分化潜力和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.