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.

当诱导细胞分化时，ES细胞具有转换为体内任何类型的细胞的潜力。此外，作为与其他类型细胞区分的显着特性之一，当在适当条件下培养细胞时，这些细胞可以无限期地传播。由于这些特性，人们可以期望ES细胞可以无限量用于许多类型的分化细胞，可用于患者的治疗。然而，作为不需要的特性，ES细胞在将细胞引入体内时会产生肿瘤，尽管该特性仅限于多能状态ES细胞。在进行这些细胞的临床使用之前，了解ES细胞水平的ES细胞的各种显着特性绝对重要。 UTF1是一种基因之一，其表达仅限于ES细胞的多能体系。我们先前使用OCT-3/4和OCT-6从分析中证明了UTF1参与ES细胞的快速生长和致肿瘤特性，而其他组则来自RNAi的实验，即UTF1对于细胞分化很重要。但是，这些数据是从非生理条件下的ES细胞中获得的，或者敲低实验，这些实验可能会破坏意外的基因表达以及UTF1基因的基因，我们决定通过产生UTF1 NULL ES细胞来检查UTF1在ES细胞中的作用。我们的数据表明，UTF1基因可以纯合中破坏，而不会显着影响任何ES细胞特异性。

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