Synergistic action of Wnt and LIF in maintaining pluripotency of mouse ES cells
Synergistic action of Wnt and LIF in maintaining pluripotency of mouse ES cells
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DOI：
10.1016/j.bbrc.2006.02.127
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发表时间：
2006-04-28
影响因子：
3.1
通讯作者：
Niwa, H
中科院分区：
文献类型：
--
作者：
Ogawa, K;Nishinakamura, R;Niwa, H
白血病抑制因子（LIF）居首位。一种可溶性因子，被鉴定为具有维持小鼠胚胎干细胞（ES）多能性的潜力。最近，第二个因素。然而，这些完全不同的信号介导的重叠功能之间的关系仍然不清楚。在这里，我们报告说，条件培养基oft-cells表达Wnt 3a维持ES细胞在无饲养层培养中的未分化状态，然后通过表达斯坦细胞标志物及其产生生殖系嵌合体的能力。然而，尽管该条件培养基的活性依赖于Wnt 3a，但重组Wnt 3a蛋白不能将ES细胞维持在未分化状态。由于单独补充Wnt 3a至LIF的亚阈值水平不足以维持ES自我更新，因此维持未分化状态的结果表明Wnt和LIF的协同作用。单独诱导组成性激活的β-连环蛋白不能维持ES自我更新，但与LIF显示出协同作用。这些观察结果表明，由经典途径介导的Wilt信号是不够的，但增强了LIF维持小鼠ES细胞自我更新的作用。(c)2006年爱思唯尔公司All rights reserved.
Leukaemia inhibitory factor (LIF) was the first. soluble factor identified as having potential to maintain the pluripotency of mouse embryonic stein (ES) cells. Recently, a second factor. Wilt, with similar activity was found. However, the relationship between these completely different signals mediating the overlapping functions is still unclear. Here, we report that the conditioned medium oft-cells expressing Wnt3a maintains ES cells in the undifferentiated state in feeder-free culture, followed by expression of stein cell markers and their ability to generate germline chimaeras. However, although the activity of this conditioned medium is dependent on Wnt3a, recombinant Wnt3a protein cannot maintain ES cells in the undifferentiated state. As supplementation with Wnt3a to the sub-threshold level of LIF alone was not sufficient to maintain ES self-renewal, the results of maintenance of the undifferentiated state indicated the synergistic action of Wnt and LIF. Induction of constitutively activated beta-catenin alone is unable to maintain ES self-renewal but shows a synergistic effect with LIF. These observations indicate that the Wilt signal mediated by the canonical pathway is not sufficient but enhances the effect of LIF to maintain self-renewal of mouse ES cells. (c) 2006 Elsevier Inc. All rights reserved.