Wisconsin Stem Cell Research Center

描述（由申请人提供）：我们最近从恒河猴，普通狨猴和人类中提取的胚胎干细胞（ES）细胞系在人类发育生物学，药物发现，药物测试和移植医学方面具有广泛的意义。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等各种细胞的能力——可能是构成身体的任何细胞类型。人类胚胎干细胞的增殖和发育潜力为体外实验研究和心脏病、帕金森氏病和白血病等疾病的移植治疗提供了基本无限的特定细胞类型。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利用人类胚胎干细胞研究其他方法难以解决的基本人类生物学问题。中心核心将提供人类胚胎干细胞组织培养支持，包括培养基制备、质量控制、成纤维细胞制备和培养的人类胚胎干细胞的常规SKY染色体分析。在资助的最后一年，将组织一个小型的重点研讨会，汇集人类胚胎干细胞研究人员和其他基础生物学家，以确定人类胚胎干细胞领域的挑战和机遇。我们建议开展以下试点项目：

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.