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Role of Jagged1-mediated Notch Signaling Activation in the Differentiation and Stratification of the Human Limbal Epithelium

机译:Jagged1介导的Notch信号传导激活在人缘上皮细胞分化和分层中的作用

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摘要

The Notch signaling pathway plays a key role in proliferation and differentiation. We investigated the effect of Jagged 1 (Jag1)-mediated Notch signaling activation in the human limbal stem/progenitor cell (LSC) population and the stratification of the limbal epithelium in vitro. After Notch signaling activation, there was a reduction in the amount of the stem/progenitor cell population, epithelial stratification, and expression of proliferation markers. There was also an increase of the corneal epithelial differentiation. In the presence of Jag1, asymmetric divisions were decreased, and the expression pattern of the polarity protein Par3, normally present at the apical-lateral membrane of basal cells, was dispersed in the cells. We propose a mechanism in which Notch activation by Jag1 decreases p63 expression at the basal layer, which in turn reduces stratification by decreasing the number of asymmetric divisions and increases differentiation.
机译:陷波信号通路在增殖和分化中起着关键作用。我们研究了锯齿状1(JAG1)介导的Notch信号传导激活在人肢茎/祖细胞(LSC)群体中的影响以及体外斜缘上皮的分层。在陷波信号激活后,茎/祖细胞群的量减少,上皮分层和增殖标志物的表达。角膜上皮分化也增加了。在jag1的存在下,不对称分裂减少,并且极性蛋白Par3的表达模式通常存在于基底细胞的顶端横向膜上分散在细胞中。我们提出了一种机制,其中JAG1的陷波激活降低了基底层的P63表达,这反过来通过降低不对称分裂的数量并增加分化来降低分层。

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