Nac1 Coordinates a Sub-network of Pluripotency Factors to Regulate Embryonic Stem Cell Differentiation.
Nac1 Coordinates a Sub-network of Pluripotency Factors to Regulate Embryonic Stem Cell Differentiation.
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DOI：
10.1016/j.celrep.2015.12.101
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发表时间：
2016-02-09
期刊：
影响因子：
8.8
通讯作者：
Gunawardena J
中科院分区：
文献类型：
--
作者：
Malleshaiah M;Padi M;Rué P;Quackenbush J;Martinez-Arias A;Gunawardena J
多能细胞在发育过程中产生不同的细胞类型，并且通常受到自我增强的分子网络的调节。这种网络如何使细胞分化还不太清楚。在这里，我们使用综合的方法来表明，外部信号诱导重组的小鼠胚胎干细胞多能性网络和四个因子的子网络-Nac 1，Oct 4，Tcf 3和Sox 2-调节其分化成替代中内胚层和神经外胚层的命运。在中内胚层的命运，Nac 1和Oct 4被限制在定量窗口内，而Sox 2和Tcf 3被抑制。与此相反，在神经外胚层的命运，Sox 2和Tcf 3受到限制，而Nac 1和Oct 4被抑制。此外，我们表明，Nac 1协调分化激活Oct 4和抑制Sox 2和Tcf 3。围绕共享因子的祖细胞网络的重组可能是一种常见的分化策略，我们的综合方法提供了一种描绘这种网络的一般方法。
Pluripotent cells give rise to distinct cell types during development and are regulated by often self-reinforcing molecular networks. How such networks allow cells to differentiate is less well understood. Here, we use integrative methods to show that external signals induce reorganization of the mouse embryonic stem cell pluripotency network and that a sub-network of four factors - Nac1, Oct4, Tcf3 and Sox2 – regulates their differentiation into the alternative mesendodermal and neuroectodermal fates. In the mesendodermal fate, Nac1 and Oct4 were constrained within quantitative windows, while Sox2 and Tcf3 were repressed. In contrast, in the neuroectodermal fate, Sox2 and Tcf3 were constrained while Nac1 and Oct4 were repressed. In addition, we show that Nac1 coordinates differentiation by activating Oct4 and inhibiting both Sox2 and Tcf3. Reorganization of progenitor cell networks around shared factors might be a common differentiation strategy and our integrative approach provides a general methodology for delineating such networks.