Activation of Akt signaling is sufficient to maintain pluripotency in mouse and primate embryonic stem cells
Activation of Akt signaling is sufficient to maintain pluripotency in mouse and primate embryonic stem cells
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DOI：
10.1038/sj.onc.1209307
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发表时间：
2006-05-04
期刊：
影响因子：
8
通讯作者：
Nakano, T
中科院分区：
文献类型：
--
作者：
Watanabe, S;Umehara, H;Nakano, T
胚胎干（ES）细胞可以无限地自我更新，而不会失去向任何细胞类型分化的能力。磷酸肌醇 3 激酶 (PI3K)/Akt 信号传导在各种干细胞系统中发挥着关键作用，包括从原始生殖细胞形成胚胎生殖 (EG) 细胞和神经干细胞的自我更新。在这里，我们证明，在不添加白血病抑制因子 (LIF) 的情况下，肉豆蔻酰化的 Akt 活性形式 (myr-Akt) 在小鼠 ES 细胞中保持未分化的表型。 myr-Akt 的作用是可逆的，因为 LIF 依赖性和多能分化活性通过删除 myr-Akt 得以恢复。此外，myr-Akt-Mer融合蛋白的酶活性受4-羟基-他莫昔芬控制，不仅维持了小鼠ES细胞的多能性，而且还维持了食蟹猴ES细胞的多能性。这些结果清楚地表明，Akt 信号传导足以维持小鼠和灵长类 ES 细胞的多能性，并支持 PI3K/Akt 信号传导轴在广泛的干细胞系统中调节“干性”的观点。
Embryonic stem (ES) cells can self-renew indefinitely without losing their differentiation ability to any cell types. Phosphoinositide-3 kinase (PI3K)/Akt signaling plays a pivotal role in various stem cell systems, including the formation of embryonic germ (EG) cells from primordial germ cells and self-renewal of neural stem cells. Here, we show that myristoylated, active form of Akt (myr-Akt) maintained the undifferentiated phenotypes in mouse ES cells without the addition of leukemia inhibitory factor (LIF). The effects of myr-Akt were reversible, because LIF dependence and pluripotent differentiation activity were restored by the deletion of myr-Akt. In addition, myr-Akt-Mer fusion protein, whose enzymatic activity is controlled by 4-hydroxy-tamoxifen, also maintained the pluripotency of not only mouse but also cynomolgus monkey ES cells. These results clearly demonstrate that Akt signaling sufficiently maintains pluripotency in mouse and primate ES cells, and support the notion that PI3K/Akt signaling axis regulates 'stemness' in a broad spectrum of stem cell systems.