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

当细胞被诱导分化时，胚胎干细胞有可能转化为体内任何类型的细胞。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，我们可以预期胚胎干细胞可以无限地提供多种类型的分化细胞，用于患者的治疗。然而，作为一种不希望的特性，胚胎干细胞被引入体内后会产生肿瘤，尽管这种特性仅限于多能状态的胚胎干细胞。在临床应用胚胎干细胞之前，了解胚胎干细胞在分子水平上的各种显著特性是非常重要的。UTF1是胚胎干细胞多能状态下表达受限的基因之一。我们之前通过Oct-3/4和Oct-6的分析证明了UTF1参与了ES细胞的快速生长和致瘤特性，而另一组通过RNAi实验表明UTF1对细胞分化很重要。然而，这些数据要么来自非生理条件下的ES细胞，要么来自可能敲除意外基因表达的敲除实验，以及UTF1基因的敲除实验，我们决定通过生成UTF1无效的ES细胞来检验UTF1在ES细胞中的作用。我们的数据表明，UTF1基因可以被纯合破坏，而不会显著影响胚胎干细胞的任何特异性。

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.