Culture Adaptation in Human Embryonic Stem Cell Lines

人类胚胎干细胞为再生医学、药物发现和毒理学提供了相当大的机会。为了实现这一潜力，需要详细了解它们的基础生物学。在过去的三到四年中，很明显，人类ES细胞可能会发生遗传和其他变化，这些变化可能会增强它们在培养物中的生长能力，当它们被维持较长时间时。我们把这个过程称为“文化适应”。该提议的基本假设是，在ES细胞的培养适应期间受影响的机制是控制这些多能干细胞的自我更新、分化和死亡之间的平衡的机制。了解适应的基础不仅可以为设计改进的方法来培养这些细胞，同时最大限度地减少变异的出现提供合理的基础，而且还可以提供控制多能干细胞自我更新的过程的见解，并提出控制其生长和分化的方法。此外，对ES细胞培养适应的理解可能会深入了解驱动畸胎癌进展的机制，畸胎癌是一种罕见的年轻男性肿瘤，也是其他基于干细胞的恶性肿瘤的范例。

Human embryonic stem (ES) cells offer considerable opportunities for regenerative medicine, drug discovery and toxicology. To realise this potential, a detailed understanding of their basic biology is required. It has become evident over the past three to four years that human ES cells may undergo genetic and other changes that may enhance their capacity for growth in culture, when they are maintained for extended periods. We have called this process, ‘culture adaptation’. The underlying hypothesis of this proposal is that the mechanisms affected during culture adaptation of ES cells are those that control the balance between self renewal, differentiation and death of these pluripotent stem cells. Understanding the basis for adaptation may not only provide a rational basis for designing improved methods to culture these cells while minimising the appearance of variants, but also may provide insights into the processes that control the self renewal of pluripotent stem cells and suggest approaches for controlling their growth and differentiation. Further, an understanding of culture adaptation of ES cells may provide insights into the mechanisms that drive progression of teratocarcinomas, a rare tumour of young men, but also a paradigm for other stem cell based malignancies.