Molecular mechanisms of the maintenance of stem cell systems

干细胞系统维持的分子机制

• 批准号: 18390088
• 负责人: NAKANO Toru
• 金额: $ 10.71万
• 依托单位: Osaka 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-18390088/
• 关键词: Stem cells; ES cells; Signal transduction; Blood cells; Cell differentiation; Reprogramming; Regenerative medicine

To analyze the molecular mechanisms of the maintenance of stem cell immaturity and those of the cell differentiation in stem cell systems, we carried out the following research.1) Function of Akt signal in the maintenance of embryonic stem cellsNuclear reprogramming' can take place by cell fusion between somatic cells with mouse embryonic stem calls (ES cells). Activation of Akt signaling in ES cells significantly promoted the efficiency of the reprogramming. In addition, the cells obtained by the cell fusion acquired the pluripotency Them results clearly demonstrate that Akt signal can maintain the pluripotency of the cells. To the contrary, Akt signaling significantly reduced the efficiency of reprogramming after somatic nuclear transfer.2) Reprogramming of blood cell differentiation by the null mutation of GATA-1GATA-1 is an essential transcription factor for erythroid differentiation. In vitro differentiation from GATA-1 null ES cells to erythroid cells gave rim to the erythroid cells. And the erythroid nails mild proliferate for long term. These erythroid cells possessed the ability to differentiate to neutrophils and macrophages. In addition, epigenetic status of the GATA-1 null erythroid cells was quite different from its wild type counterpart. This result clearly demonstrate that this experimental system is an excellent model system to analyze the epigenetic modification by transcription factors.

为了分析干细胞系统中维持干细胞不成熟和细胞分化的分子机制，我们进行了以下研究：1）Akt信号在维持胚胎干细胞中的作用细胞可以发生“核重编程”体细胞与小鼠胚胎干细胞（ES细胞）之间的融合。 ES 细胞中 Akt 信号的激活显着提高了重编程的效率。此外，细胞融合获得的细胞获得了多能性。结果清楚地表明Akt信号可以维持细胞的多能性。相反，Akt信号显着降低了体细胞核移植后重编程的效率。2)GATA-1无效突变引起的血细胞分化重编程GATA-1是红细胞分化的重要转录因子。从 GATA-1 缺失 ES 细胞到类红细胞的体外分化产生了类红细胞的边缘。且红系指甲长期轻度增殖。这些红细胞具有分化为中性粒细胞和巨噬细胞的能力。此外，GATA-1无效红系细胞的表观遗传状态与其野生型对应物有很大不同。这一结果清楚地表明该实验系统是分析转录因子表观遗传修饰的优秀模型系统。

项目成果

PGC7/Stella protects against DNA demethylation in early embryogenesis

• DOI: 10.1038/ncb1519
• 发表时间: 2007-01-01
• 期刊: NATURE CELL BIOLOGY
• 影响因子: 21.3
• 作者: Nakamura, Toshinobu;Arai, Yoshikazu;Nakano, Toru
• 通讯作者: Nakano, Toru

Akt activation induces epidermal hyperplasia and proliferation of epiderthal progenitors

Akt 激活诱导表皮增生和表皮祖细胞增殖

• 发表时间: 2007
• 期刊: Oncogene 26
• 作者: Murayama;K;Kimura;T;Tarutani;M;Tomooka;M;Hayashi;R;Okabe;M;Nishida;K;Itami;S;Katavama;I;Nakano;T
• 通讯作者: T

Characterization of the piRNA complex from rat testes

• DOI: 10.1126/science.1130164
• 发表时间: 2006-07-21
• 期刊: SCIENCE
• 影响因子: 56.9
• 作者: Lau, Nelson C.;Seto, Anita G.;Kingston, Robert E.
• 通讯作者: Kingston, Robert E.

Activation of Akt signaling is sufficient to maintain pluripotency in mouse and primate embryonic stem cells

• DOI: 10.1038/sj.onc.1209307
• 发表时间: 2006-05-04
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Watanabe, S;Umehara, H;Nakano, T
• 通讯作者: Nakano, T

Pten/PI3K pathway governs the homeostasis of Valphal4iNKT cells

Pten/PI3K 通路调控 Valphal4iNKT 细胞的稳态

• 发表时间: 2007
• 期刊: Blood 109
• 作者: Kishimoto;H;Ohteki;T;Yajima;N;Kawahara;K;Natsui;M;Kawarasaki;S;Hamada;K;Horie;Y;Kubo;Y;Arase;S;Taniguchi;M;Vanhaesebroeck;B;Mak;TW.;Nakano;T.;Kovasu;S.;Sasaki;T.;Suzuki
• 通讯作者: Suzuki