Regulation of neural stem/progenitor cell maintenance by PI3K and mTOR
Regulation of neural stem/progenitor cell maintenance by PI3K and mTOR
复制标题
DOI：
10.1016/j.neulet.2009.12.067
复制
发表时间：
2010-02
影响因子：
2.5
通讯作者：
A. Sato;Jun Sunayama;Ken‐ichiro Matsuda;K. Tachibana;K. Sakurada;A. Tomiyama;T. Kayama;C. Kitanaka
中科院分区：
文献类型：
--
作者：
A. Sato;Jun Sunayama;Ken‐ichiro Matsuda;K. Tachibana;K. Sakurada;A. Tomiyama;T. Kayama;C. Kitanaka
控制干细胞状态和神经干/祖细胞的分化对于神经系统的正常发育是必不可少的。EGF和FGF 2在神经干/祖细胞的调控中发挥重要作用，但其机制尚不清楚。在这里，我们表明，使用小鼠神经干细胞/祖细胞的体外原代培养物，PI 3 K和mTOR都被EGF/FGF 2激活，但单独抑制PI 3 K或mTOR的激活仅导致神经干细胞/祖细胞增殖减少，而不影响其干细胞状态，即自我更新的能力。然而，重要的是，PI 3 K和mTOR的同时抑制促进退出干细胞状态以及神经干/祖细胞的星形胶质细胞分化。这些发现表明，PI 3 K和mTOR参与EGF/FGF 2介导的神经干/祖细胞的维持，并且它们可能以平行和独立的途径起作用，相互补充和支持以维持干细胞状态。
Control of stem cell state and differentiation of neural stem/progenitor cells is essential for proper development of the nervous system. EGF and FGF2 play important roles in the control of neural stem/progenitor cells, but the underlying mechanism still remains unclear. Here we show, using in vitro primary cultures of mouse neural stem/progenitor cells, that both PI3K and mTOR are activated by EGF/FGF2 but that inhibiting the activation of either PI3K or mTOR alone results in only reduced proliferation of neural stem/progenitor cells without affecting their stem cell state, namely, the capacity to self-renew. However, significantly, concurrent inhibition of PI3K and mTOR promoted exit from the stem cell state together with astrocytic differentiation of neural stem/progenitor cells. These findings suggest that PI3K and mTOR are involved in the EGF/FGF2-mediated maintenance of neural stem/progenitor cells and that they may act in parallel and independent pathways, complementing and backing up each other to maintain the stem cell state.