Wisconsin Stem Cell Research Center

威斯康星干细胞研究中心

• 批准号: 6805557
• 负责人: James A Thomson
• 金额: $ 74.94万
• 依托单位: WICELL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6805557
• 关键词: cell differentiation; embryonic stem cell; gene expression

DESCRIPTION (provided by applicant): Our recent derivation of embryonic stem (ES) cell lines from rhesus monkeys, common marmosets, and humans has widespread implications for human developmental biology, drug discovery, drug testing, and transplantation medicine. After months or years of growth in culture dishes, these cells retain the ability to form cells ranging from heart muscle to nerve to blood--potentially any cell type that makes up the body. The proliferative and developmental potential of human ES cells promises an essentially unlimited supply of specific cell types for in vitro experimental studies and for transplantation therapies for diseases such as heart disease, Parkinson's disease, and leukemia. In the long run, however, the greatest legacy for human ES cells may be not as a source of tissue for transplantation medicine, but as a basic research tool to understand the human body. This new tool will be particularly important for lineages that differ significantly between humans and mice. The Exploratory Center for Human Embryonic Stem Cell Research proposed here will begin to focus on using human ES cells to study questions in basic human biology that are not easily addressed by other approaches. A center core will provide human ES cell tissue culture support, including media preparation, quality control, fibroblast preparation, and routine SKY chromosomal analysis of cultured human ES cells. In the final year of funding, a small, focused workshop will be organized to bring together human ES cell researchers and other basic biologists to identify challenges and opportunities in the human ES cell field. We propose the following Pilot Projects: (I) We will analyze the transciptional changes in one important early lineage: the transition from human ES cell to primitive ectoderm to neural ectoderm to differentiated neurons. (II) We will analyze the transcriptional control of how BMP4 causes human ES cells to exit self-renewal and differentiate to trophoblast, using expression cloning strategies and iRNA to add and subtract function. (III) We will use a biochemical approach, coupled with cutting-edge mass spectrometry and proteomics, to identify those factors produced by fibroblasts that mediate human ES cell self-renewal.

描述（由申请人提供）：我们最近从恒河猴、普通绒猴和人类获得的胚胎干（ES）细胞系对人类发育生物学、药物发现、药物测试和移植医学具有广泛的意义。在培养皿中生长数月或数年后，这些细胞保留了形成从心肌到神经到血液的细胞的能力-可能是构成身体的任何细胞类型。人ES细胞的增殖和发育潜力保证了特定细胞类型的基本上无限的供应，用于体外实验研究和用于疾病如心脏病、帕金森病和白血病的移植治疗。然而，从长远来看，人类胚胎干细胞最大的遗产可能不是作为移植医学的组织来源，而是作为了解人体的基础研究工具。这种新工具对于人类和小鼠之间存在显著差异的谱系尤其重要。这里提出的人类胚胎干细胞研究探索中心将开始专注于使用人类ES细胞研究其他方法不容易解决的基础人类生物学问题。中心核心将提供人ES细胞组织培养支持，包括培养基制备、质量控制、成纤维细胞制备和培养的人ES细胞的常规SKY染色体分析。在资助的最后一年，将组织一个小型的、有重点的研讨会，将人类ES细胞研究人员和其他基础生物学家聚集在一起，以确定人类ES细胞领域的挑战和机遇。我们建议开展以下试点项目： (I)我们将分析一个重要的早期谱系中的转录变化：从人ES细胞到原始外胚层到神经外胚层再到分化的神经元的转变。(II)我们将分析BMP 4如何导致人类ES细胞退出自我更新和分化为滋养层的转录控制，使用表达克隆策略和iRNA添加和减去功能。(III)我们将使用生物化学方法，加上尖端的质谱和蛋白质组学，以确定那些由成纤维细胞介导人类ES细胞自我更新的因素。