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A protein interaction network for pluripotency of embryonic stem cells

机译：胚胎干细胞多能性的蛋白质相互作用网络

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摘要

Embryonic stem ( ES) cells are pluripotent(1,2) and of therapeutic potential in regenerative medicine(3,4). Understanding pluripotency at the molecular level should illuminate fundamental properties of stem cells and the process of cellular reprogramming. Through cell fusion the embryonic cell phenotype can be imposed on somatic cells, a process promoted by the homeodomain protein Nanog(5), which is central to the maintenance of ES cell pluripotency(6,7). Nanog is thought to function in concert with other factors such as Oct4 ( ref. 8) and Sox2 ( ref. 9) to establish ES cell identity. Here we explore the protein network in which Nanog operates in mouse ES cells. Using affinity purification of Nanog under native conditions followed by mass spectrometry, we have identified physically associated proteins. In an iterative fashion we also identified partners of several Nanog- associated proteins ( including Oct4), validated the functional relevance of selected newly identified components and constructed a protein interaction network. The network is highly enriched for nuclear factors that are individually critical for maintenance of the ES cell state and co- regulated on differentiation. The network is linked to multiple co- repressor pathways and is composed of numerous proteins whose encoding genes are putative direct transcriptional targets of its members. This tight protein network seems to function as a cellular module dedicated to pluripotency.
机译：胚胎干细胞（ES）具有多能性（1,2），在再生医学中具有治疗潜力（3,4）。在分子水平上了解多能性应该阐明干细胞的基本特性和细胞重编程的过程。通过细胞融合，可以将胚细胞表型强加于体细胞上，这一过程是由同源域蛋白Nanog（5）促进的，这是维持ES细胞多能性的关键（6,7）。 Nanog被认为可以与其他因素（例如Oct4（参考文献8）和Sox2（参考文献9））协同工作，以建立ES细胞身份。在这里，我们探讨了Nanog在小鼠ES细胞中运作的蛋白质网络。通过在自然条件下对Nanog进行亲和纯化，然后进行质谱分析，我们已经鉴定出了物理相关的蛋白质。我们还以迭代的方式确定了几种与Nanog相关的蛋白质（包括Oct4）的伙伴，验证了所选新鉴定成分的功能相关性，并构建了蛋白质相互作用网络。该网络高度丰富了核因子，这些因子对于维持ES细胞状态至关重要，并且在分化过程中受到共同调节。该网络与多种共抑制通路相连，并由众多蛋白质组成，这些蛋白质的编码基因是其成员的假定直接转录靶标。这种紧密的蛋白质网络似乎起着致力于多能性的细胞模块的作用。

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