Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells.
Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells.
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DOI：
10.1038/ncb2314
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发表时间：
2011-08-14
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
--
作者：
多能干细胞存在于初始状态和启动状态，由小鼠胚胎干细胞（ESCs）和发育更高级的外胚层干细胞（EpiSCs；参考文献）形成。在胚胎干细胞的初始状态下，基因组具有不寻常的开放构象，并且具有最小的抑制表观遗传标记。相反，EpiSCs激活了支持胚胎细胞类型分化的表观遗传机制。因此，从幼稚多能性到引物多能性的转变代表了细胞分化的关键事件。但控制这一基本分化步骤的信号仍不清楚。我们在这里表明，旁分泌和自分泌Wnt信号是ESCs必不可少的自我更新因子，并且需要抑制它们向epscs分化。此外，我们发现Wnt蛋白与细胞因子LIF结合足以在没有任何未定义因素的情况下支持ESC自我更新，并支持新的ESC系的衍生，包括来自非允许小鼠品系的ESC系。我们的研究结果不仅证明了Wnt信号调节了原始到启动的多能性转变，而且还确定了Wnt是一个必要的和限制性的ESC自我更新因子。
Pluripotent stem cells exist in naive and primed states, epitomized by mouse embryonic stem cells (ESCs) and the developmentally more advanced epiblast stem cells (EpiSCs; ref.). In the naive state of ESCs, the genome has an unusual open conformation and possesses a minimum of repressive epigenetic marks. In contrast, EpiSCs have activated the epigenetic machinery that supports differentiation towards the embryonic cell types. The transition from naive to primed pluripotency therefore represents a pivotal event in cellular differentiation. But the signals that control this fundamental differentiation step remain unclear. We show here that paracrine and autocrine Wnt signals are essential self-renewal factors for ESCs, and are required to inhibit their differentiation into EpiSCs. Moreover, we find that Wnt proteins in combination with the cytokine LIF are sufficient to support ESC self-renewal in the absence of any undefined factors, and support the derivation of new ESC lines, including ones from non-permissive mouse strains. Our results not only demonstrate that Wnt signals regulate the naive-to-primed pluripotency transition, but also identify Wnt as an essential and limiting ESC self-renewal factor.
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影响因子：
23.9
作者：
Hayashi K;de Sousa Lopes SMC;Tang F;Lao K;Surani MA
通讯作者：
Surani MA
DOI：
10.1073/pnas.96.7.3546
发表时间：
1999-03-30
影响因子：
11.1
作者：
Hsieh, JC;Rattner, A;Nathans, J
通讯作者：
Nathans, J
影响因子：
5.3
作者：
Lustig, B;Jerchow, B;Behrens, J
通讯作者：
Behrens, J
影响因子：
64.8
作者：
Brons, I. Gabrielle M.;Smithers, Lucy E.;Vallier, Ludovic
通讯作者：
Vallier, Ludovic
影响因子：
23.9
作者：
Nichols, Jennifer;Smith, Austin
通讯作者：
Smith, Austin