Intrinsic transition of embryonic stem-cell differentiation into neural progenitors
Intrinsic transition of embryonic stem-cell differentiation into neural progenitors
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DOI：
10.1038/nature09726
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发表时间：
2011-02-24
期刊：
影响因子：
64.8
通讯作者：
Sasai, Yoshiki
中科院分区：
文献类型：
--
作者：
Kamiya, Daisuke;Banno, Satoe;Sasai, Yoshiki
胚胎干细胞（embryonic stem cell，ES细胞）的分化方向通常被认为是神经元的命运。然而，很少有人知道的细胞内机制，导致未分化的细胞采用的神经命运的外在诱导信号的情况下。在这里，我们表明，锌指核蛋白Zfp521是必不可少的，足以驱动小鼠ES细胞的内在神经分化。在不存在神经分化抑制剂BMP 4的情况下，在分化的ES细胞中内在地诱导强Zfp521表达。Zfp521的强制表达即使在BMP 4存在下也能够实现ES细胞的神经转化。相反，在分化培养中，Zfp521耗尽的ES细胞不经历神经转化，而是倾向于停止在外胚层状态。Zfp521通过与辅激活因子p300共同作用直接激活早期神经基因。因此，ES细胞从外胚层状态分化为神经外胚层祖细胞的转变特别依赖于Zfp521的细胞内在表达和激活剂功能。
The neural fate is generally considered to be the intrinsic direction of embryonic stem (ES) cell differentiation. However, little is known about the intracellular mechanism that leads undifferentiated cells to adopt the neural fate in the absence of extrinsic inductive signals. Here we show that the zinc-finger nuclear protein Zfp521 is essential and sufficient for driving the intrinsic neural differentiation of mouse ES cells. In the absence of the neural differentiation inhibitor BMP4, strong Zfp521 expression is intrinsically induced in differentiating ES cells. Forced expression of Zfp521 enables the neural conversion of ES cells even in the presence of BMP4. Conversely, in differentiation culture, Zfp521-depleted ES cells do not undergo neural conversion but tend to halt at the epiblast state. Zfp521 directly activates early neural genes by working with the co-activator p300. Thus, the transition of ES cell differentiation from the epiblast state into neuroectodermal progenitors specifically depends on the cell-intrinsic expression and activator function of Zfp521.