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

胚胎干细胞特异性辅激活因子UTF1对ES细胞致瘤特性的作用

• 批准号: 18390106
• 负责人: OKUDA Akihiko
• 金额: $ 10.77万
• 依托单位: Saitama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390106/
• 关键词: embryonic stem cells; pluripotency; tumorigenic property; cellular differentiation; cell growth; teratoma; gene targeting; UTF1; ジーンタゲティング; 全能性; 自己増殖性; 分化誘導; ジーンテゲティング; ノックアウトマウス

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.

当细胞被诱导分化时，ES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着特性之一，当细胞在适当的条件下培养时，这些细胞可以无限增殖。由于这些特性，人们可以预期ES细胞可以无限地供应多种类型的分化细胞，用于患者的治疗。然而，作为一种不需要的特性，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。在临床使用这些细胞之前，在分子水平上了解 ES 细胞的各种显着特性绝对是重要的。 UTF1是其表达仅限于ES细胞多能状态的基因之一。我们之前通过Oct-3/4和Oct-6的分析证明UTF1参与ES细胞的快速生长和致瘤特性，而其他小组通过RNAi实验表明UTF1对于细胞分化很重要。然而，这些数据要么是从非生理条件下的ES细胞中获得的，要么是敲除实验中获得的，敲低实验可能会敲除意外的基因表达以及UTF1基因的表达，我们决定通过生成UTF1来检查UTF1在ES细胞中的作用无效 ES 细胞。我们的数据表明，UTF1 基因可以被纯合性破坏，而不会显着影响任何 ES 细胞特异性特性。

项目成果

Role of Nucleostemin in ES cells and Somatic Stem Cells

Nucleostemin 在 ES 细胞和成体干细胞中的作用

• 发表时间: 2007
• 作者: Jun;Nomura
• 通讯作者: Nomura

Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells

• DOI: 10.1038/ncb1589
• 发表时间: 2007-06-01
• 期刊: NATURE CELL BIOLOGY
• 影响因子: 21.3
• 作者: Masui, Shinji;Nakatake, Yuhki;Niwa, Hitoshi
• 通讯作者: Niwa, Hitoshi

The Sox2 regulatory region 2 functions as a neural stem cell-specific enhancer in the telencephalon

• DOI: 10.1074/jbc.m512669200
• 发表时间: 2006-05-12
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Miyagi, S;Nishimoto, M;Okuda, A
• 通讯作者: Okuda, A

Expression of pluripotency marker, UTF1, is restricted to a subpopulation of early A spermatogonia in rat testis

多能性标记 UTF1 的表达仅限于大鼠睾丸中早期 A 精原细胞的亚群

• 发表时间: 2008
• 期刊: Reproduction 136
• 作者: Miyoshi T.;Kanoh J.;Saito M. and Ishikawa F;Junko Kanoh;Naoko Ohtani;Kanoh J;Eiji Hara;Keiichiro Suzuki;Hiromitsu kajiyama;Jun Nomura;Satoru Mivagi;Maaike P A van Bragt
• 通讯作者: Maaike P A van Bragt

Nucleostemin遺伝子の各種幹細胞における機能

Nucleostemin基因在多种干细胞中的功能

• 发表时间: 2007
• 作者: Horiba;M.;Kadomatsu;K.;Yasui;K.;Lee;J.;Takenaka;H.;Sumida;A.;Kamiya;K.;Chen;S.;Sakuma;S.;Muramatsu;T.;Kodama;I.;野村 淳
• 通讯作者: 野村 淳