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，这些细胞在适当条件下培养时可以无限增殖。由于这些特性，人们可以预期ES细胞可以成为许多类型的分化细胞的无限供应者，这些分化细胞可以用于患者的治疗。然而，作为不需要的特性，ES细胞在被引入体内时产生肿瘤，尽管该特性仅限于多能状态的ES细胞。在临床应用ES细胞之前，在分子水平上了解ES细胞的各种显著特性是非常重要的。UTF 1基因是ES细胞多能性表达的基因之一。我们之前已经从使用Oct-3/4和Oct-6的分析中证明UTF 1参与ES细胞的快速生长和致瘤特性，而其他小组从RNAi实验中提出UTF 1对细胞分化是重要的。然而，这些数据是从非生理条件下的ES细胞或敲除实验中获得的，敲除实验可能敲除意外的基因表达以及UTF 1基因的表达，我们决定通过产生UTF 1缺失的ES细胞来检查UTF 1在ES细胞中的作用。我们的数据表明，UTF 1基因可以被同源性破坏，而不影响任何ES细胞特异性的性质显着。

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.