Role of cell-cell adhesion complexes in embryonic stem cell biology
Role of cell-cell adhesion complexes in embryonic stem cell biology
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DOI：
10.1242/jcs.146720
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发表时间：
2014-06-15
影响因子：
4
通讯作者：
van Roy, Frans
中科院分区：
文献类型：
--
作者：
Pieters, Tim;van Roy, Frans
多能胚胎干细胞（ESCs）能够自我更新或分化为生物体内的任何细胞类型。在此，我们聚焦于钙黏蛋白和连环蛋白（它们的胞质支架蛋白）在哺乳动物胚胎干细胞的命运、维持和分化中所起的作用。E - 钙黏蛋白是一种主要的干细胞调节因子，对于小鼠胚胎干细胞（mESC）的维持和分化均是必需的。E - 钙黏蛋白与原始干性通路的关键组分相互作用，去除它会阻止干细胞形成分化良好的畸胎瘤或参与嵌合动物的形成。此外，耗尽E - 钙黏蛋白会使原始的小鼠胚胎干细胞转变为始发态上胚层样干细胞（EpiSCs）。与此一致的是，在体细胞重编程为诱导多能干细胞（iPSCs）的过程中会发生间充质向上皮转化（MET），导致N - 钙黏蛋白下调以及E - 钙黏蛋白水平升高。β - 连环蛋白具有双重功能；它在基于钙黏蛋白的黏附以及WNT信号传导中起作用，尽管WNT信号传导对干性很重要，但β - 连环蛋白的黏附功能对于维持干细胞的原始状态可能至关重要。此外，越来越多的证据表明其他连接蛋白在胚胎干细胞生物学中也很重要。因此，几种连接蛋白（特别是E - 钙黏蛋白）精确调控的水平和活性保障了原始多能性，并且是体细胞完全重编程的先决条件。
Pluripotent embryonic stem cells (ESCs) can self-renew or differentiate into any cell type within an organism. Here, we focus on the roles of cadherins and catenins - their cytoplasmic scaffold proteins - in the fate, maintenance and differentiation of mammalian ESCs. E-cadherin is a master stem cell regulator that is required for both mouse ESC (mESC) maintenance and differentiation. E-cadherin interacts with key components of the naive stemness pathway and ablating it prevents stem cells from forming well-differentiated teratomas or contributing to chimeric animals. In addition, depleting E-cadherin converts naive mouse ESCs into primed epiblast-like stem cells (EpiSCs). In line with this, a mesenchymal-to-epithelial transition (MET) occurs during reprogramming of somatic cells towards induced pluripotent stem cells (iPSCs), leading to downregulation of N-cadherin and acquisition of high E-cadherin levels. beta-catenin exerts a dual function; it acts in cadherin-based adhesion and in WNT signaling and, although WNT signaling is important for stemness, the adhesive function of beta-catenin might be crucial for maintaining the naive state of stem cells. In addition, evidence is rising that other junctional proteins are also important in ESC biology. Thus, precisely regulated levels and activities of several junctional proteins, in particular E-cadherin, safeguard naive pluripotency and are a prerequisite for complete somatic cell reprogramming.