Role of telomerase on stem cells

端粒酶对干细胞的作用

• 批准号: 18590058
• 负责人: IDE Toshinori
• 金额: $ 2.57万
• 依托单位: Hiroshima International University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-18590058/
• 关键词: stem cells; hTERT; telomerase; telomere; cell life-span; immortal cells; celllar senescence; 細胞不死化; 血管内皮細胞; ヒト培養細胞; 肝実質細胞; 間葉系幹細胞; ヒト細胞

Stem cells have three prominent characteristics, i.e., telomerase activity, unlimited proliferative life-span and ability to differentiate. Telomerase is an enzyme that elongates telomere sequences at each chromosome end and allows cells to proliferate indefinitely. Several lines of fragmental evidence, however, suggest that telomerase has additional roles for the maintenance of characteristics seen in stem cells. Premature senescence of cultured human fibroblasts was induced by continuous treatment with low concentrations of hydrogen peroxide, which was not observed in hTERT (human telomerase gene)-introduced fibroblasts under the same condition. To have some idea on the role of telomerase on the bypass of premature senescence, we searched for possible differences on signal transduction process during cell response between normal fibroblasts and hTERT-introduced fibroblasts and between cellular senescence and premature senescence. Enhancement of p21 was observed according to the progression of both cellular senescence and premature senescence of human fibroblasts, which was confirmed by reporter assay using p21 promoter conjugated by reporter gene. Enhancement of p21 was weak, if not at all, in hTERT-introduced cells which bypassed cellular senescence and premature senescence. We could not find the reason why hTERT-expressing fibroblasts bypassed premature senescence under which normal fibroblasts ceased proliferation.

干细胞具有端粒酶活性、无限增殖寿命和分化能力三大显着特征。端粒酶是一种酶，可以延长每个染色体末端的端粒序列，并使细胞无限增殖。然而，一些零碎的证据表明，端粒酶对于维持干细胞特征具有额外的作用。用低浓度过氧化氢连续处理可诱导培养的人成纤维细胞过早衰老，而在相同条件下导入hTERT（人端粒酶基因）的成纤维细胞中未观察到这种情况。为了了解端粒酶在绕过过早衰老中的作用，我们寻找正常成纤维细胞和引入hTERT的成纤维细胞之间以及细胞衰老和过早衰老之间的细胞反应过程中信号转导过程可能存在的差异。根据细胞衰老和人成纤维细胞过早衰老的进展观察到p21的增强，这通过使用报告基因缀合的p21启动子的报告测定来证实。在绕过细胞衰老和过早衰老的引入 hTERT 的细胞中，p21 的增强即使没有增强，也是微弱的。我们无法找到表达 hTERT 的成纤维细胞绕过正常成纤维细胞停止增殖的过早衰老的原因。

项目成果

hTERTによるヒト血管内皮細胞におけるテロメアG-tailの延長と正常細胞の機能維持

hTERT 延长人血管内皮细胞端粒 G 尾并维持正常细胞功能

• 发表时间: 2007
• 作者: 福崎;笑子;Kumiko Anno;Teruyuki Kajiume;井出 利憲;Kumiko Anno;Kumiko Anno;Teruyuki Kajiume;井出利憲ほか5名;井出利憲ほか10名;Hidetoshi Tahara;Louis Yuge;Akiko Takahashi;Yumi Kawahara;田原 栄俊;井出 利憲;井出 利憲;井出 利憲;井出 利憲;Hidetoshi Tahara;Akiko Takahashi;Yumi Kawahara;井出利憲ほか6名;井出利憲ほか9名;井出利憲;井出利憲;阿武 久美子
• 通讯作者: 阿武 久美子

内因性細胞老化(老化時計)

内在细胞衰老（衰老时钟）

• 发表时间: 2006
• 期刊: 肝, 胆, 膵 55
• 作者: 福崎;笑子;Kumiko Anno;Teruyuki Kajiume;井出 利憲;Kumiko Anno;Kumiko Anno;Teruyuki Kajiume;井出利憲ほか5名;井出利憲ほか10名;Hidetoshi Tahara;Louis Yuge;Akiko Takahashi;Yumi Kawahara;田原 栄俊;井出 利憲;井出 利憲
• 通讯作者: 井出 利憲

Mitogenic signalling and the p16^<ink4a>-Rb pathway cooperate to enforce irreversible cellular senescence through activating ROS/PKC-delta signalling pathway.

有丝分裂信号传导和 p16^<ink4a>-Rb 通路协同作用，通过激活 ROS/PKC-delta 信号通路来强制不可逆的细胞衰老。

• 发表时间: 2006
• 期刊: Nature Cell Biology 8
• 作者: 福崎;笑子;Kumiko Anno;Teruyuki Kajiume;井出 利憲;Kumiko Anno;Kumiko Anno;Teruyuki Kajiume;井出利憲ほか5名;井出利憲ほか10名;Hidetoshi Tahara;Louis Yuge;Akiko Takahashi;Yumi Kawahara;田原 栄俊;井出 利憲;井出 利憲;井出 利憲;井出 利憲;Hidetoshi Tahara;Akiko Takahashi;Yumi Kawahara;井出利憲ほか6名;井出利憲ほか9名
• 通讯作者: 井出利憲ほか9名

Floating culture promotes the maintenance of hematopoietic stem cells

• DOI: 10.1016/j.febslet.2007.08.057
• 发表时间: 2007-10-02
• 期刊: FEBS LETTERS
• 影响因子: 3.5
• 作者: Kajiume, Teruyuki;Yuge, Louis;Kobayashi, Masao
• 通讯作者: Kobayashi, Masao

Novel electrical stimulation sets the cultured myoblast contractile function to 'on'

• DOI: 10.1159/000099123
• 发表时间: 2006-01-01
• 期刊: PATHOBIOLOGY
• 影响因子: 5
• 作者: Kawahara, Yumi;Yamaoka, Kaoru;Yuge, Louis
• 通讯作者: Yuge, Louis