Role of embryonic stem cell-specific coacitvator UTF1 for tumorigenic property of ES cells

当细胞被诱导分化时，ES细胞具有转化为体内任何类型细胞的潜力。此外，作为区别于其他类型细胞的显著特性之一，当细胞在适当的条件下培养时，这些细胞可以无限繁殖。由于这些特性，可以预期ES细胞可以无限提供多种类型的分化细胞，用于患者的治疗。然而，作为一种不受欢迎的特性，ES细胞在被引入体内时会产生肿瘤，尽管这种特性仅限于多能状态的ES细胞。在进行ES细胞的临床应用之前，在分子水平上了解ES细胞的各种显着特性是非常重要的。UTF1是表达仅限于多能状态的ES细胞的基因之一。我们之前已经从Oct-3/4和Oct-6的分析中证明了UTF1参与了ES细胞的快速生长和致瘤特性，而另一个小组通过RNAi实验表明UTF1对细胞分化很重要。然而，这些数据是从非生理条件下的ES细胞获得的，或者是可能下调UTF1基因表达的敲除实验，我们决定通过产生UTF1缺失的ES细胞来检测UTF1在ES细胞中的作用。我们的数据表明，UTF1基因可以被纯合子破坏，而不会显著影响任何ES细胞的特异性。

ES cells have potentials to convert to any types of cells in the body when cells are induced to differentiate. Furthermore, as one of remarkable properties discriminating from other types of cells, these cells can propagate indefinitely when the cells are cultured under appropriate conditions. Because of these properties, one can expect that ES cells can be unlimited supplier for many types of differentiated cells which can be used for patients' treatment. However, as an unwanted property, ES cells produce tumor when the cells are introduced into body, albeit this property is restricted to pluripotent state ES cells. It is definitely important to understand the various remarkable properties of ES cells in molecular levels before performing clinical use of these cells. UTF1 is one of genes whose expression is restricted to pluripotent sate of ES cells. We have previously demonstrated from the analyses using Oct-3/4 and Oct-6 that UTF1 is involve in rapid growth and tumorigenic properties of ES cell, while other group suggested from experiments with RNAi that UTF1 is important for cell differentiation. However, these data were obtained either from ES cells which are under non-physiological conditions or knock down experiments which may knock down unexpected gene expression as well as that of UTF1 gene, we decided to examine the role of UTF1 in ES cells by generating UTF1 null ES cells. Our data implicate that UTF1 gene can be disrupted homozygously without affecting any ES cell-specific properties significantly.