WNT/β-catenin pathway up-regulates Stat3 and converges on LIF to prevent differentiation of mouse embryonic stem cells
WNT/β-catenin pathway up-regulates Stat3 and converges on LIF to prevent differentiation of mouse embryonic stem cells
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DOI：
10.1016/j.ydbio.2005.11.011
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发表时间：
2006-02-01
影响因子：
2.7
通讯作者：
Zhao, GQ
中科院分区：
文献类型：
--
作者：
Hao, J;Li, TG;Zhao, GQ
胚胎干细胞依靠供体细胞或外源细胞提供的油脂生长因子来维持其多能性。为了确定这些因素，我们建立了STO饲养细胞的子系，这些子系在支持ES细胞自我更新方面表现出不同的能力。功能筛选发现WNT5A和WNT6是STO细胞产生的因子，以血清依赖的方式有效抑制ES细胞分化。此外，在不干扰WNT/ β -catenin通路上游组分的情况下，直接激活β -catenin完全再现了WNT对ES细胞的作用。重要的是，WNT/ β -catenin通路上调Stat3 mRNA， Stat3是小鼠胚胎干细胞自我更新的已知调节剂。最后，LIF能够模拟血清效应，与WNT蛋白协同作用，抑制ES细胞分化。因此，我们的研究揭示了WNT/ β -catenin通路在STAT3水平上通过趋同LIF/JAK-STAT通路阻止ES细胞分化的部分分子机制。(c) 2005爱思唯尔公司版权所有。
Embryonic stem (ES) cells rely oil growth factors provided by feeder cells or exogenously to maintain their pluripotency. In order to identify such factors, we have established sub-lines of STO feeder cells which exhibit variable ability in supporting ES cell self-renewal. Functional screening identifies WNT5A and WNT6 as STO cell-produced factors that potently inhibit ES cell differentiation in a serum-dependent manner. Furthermore, direct activation of beta-catenin without disturbing the upstream components of the WNT/beta-catenin pathway fully recapitulates the effect of WNTs on ES cells. Importantly, the WNT/beta-catenin pathway up-regulates the mRNA for Stat3, a known regulator of ES cell self-renewal in the mouse. Finally, LIF is able to mimic the serum effect to act synergistically with WNT proteins to inhibit ES cell differentiation. Therefore, our study reveals part of the molecular mechanisms by which the WNT/beta-catenin pathway acts to prevent ES cell differentiation through convergence on the LIF/JAK-STAT pathway at the level of STAT3. (c) 2005 Elsevier Inc. All rights reserved.