Control of growth and differentiation of normal and malignant human pluripotent stem cells

人类胚胎干细胞（ES细胞）是来源于早期胚胎的细胞，其可以在原始胚胎状态下在培养物中无限期生长，同时保留它们所来源的胚胎细胞的关键特征：多能性，或产生任何类型的成体组织细胞的能力。由于ES细胞代表了任何类型的人类细胞的无限来源，它们在功能基因组学和药物发现等研究领域以及再生医学中具有巨大的潜力，使用移植组织来治愈退行性疾病。我们的实验室是世界上两个开发人类胚胎干细胞的实验室之一，也是第一个在体外证明这些细胞分化为专门的细胞-神经元的实验室。为了使用ES细胞，我们需要更多地了解如何在实验室中培养和操作它们，以及如何将它们转化为所需类型的体细胞。我们的研究是基于这样的假设，即人类ES细胞的生长控制类似于胚胎的生长控制，干细胞和它们分化的后代之间的相互作用由来自膜结合或可溶性蛋白质的信号介导，指导干细胞的分化。我们最近已经确定了几个关键的蛋白质调节人ES细胞。本项目将利用高通量基因表达分析来确定更多的候选调控蛋白。然后，我们将使用我们实验室开发的细胞培养系统和技术来确定这些蛋白质如何控制干细胞生长。这些研究将大大提高控制干细胞的能力，并将其转化为专门的细胞类型，用于研究和再生医学。这些进展是必不可少的，如果胚胎干细胞要从目前的状态，作为一个有趣的实验室现象，成为一个强大的工具，为研究和医学。

Human embryonic stem cells (ES cells) are cells derived from the early embryo which can be grown in culture for indefinite periods in the primitive embryonic state, while retaining a key feature of the embryonic cells from which they were derived: pluripotentiality, or the ability to give rise to any type of adult tissue cell. Because ES cells represent an unlimited source of any type of human cell, they have great potential for use in research areas such as functional genomics and drug discovery, and in regenerative medicine, the use of transplanted tissue to cure degenerative disease. Our laboratory is one of two in the world to develop human ES cells and the first to demonstrate differentiation of these cells into specialised cells-neurons- in vitro. In order to use ES cells, we need to learn more about how to grow and manipulate them in the laboratory, and how to turn them into desired types of somatic cell. Our study is based on the hypothesis that growth control in human ES cells resembles growth control in the embryo, with interactions between stem cells and their differentiated offspring mediated by signals from membrane bound or soluble proteins directing the differentiation of the stem cells. We have recently identified several key protein regulators of human ES cells. This project will use high throughput analysis of gene expression to pinpoint more candidate regulatory proteins. Then we will use cell culture systems and techniques developed in our laboratory to determine how these proteins may act to control stem cell growth. These studies will result in a greatly improved ability to control stem cells and turn them into specialised cell types for use in research and regenerative medicine. These advances are essential if ES cells are to progress from their current status as an interesting laboratory phenomenon to become a powerful tool for research and medicine.