The tight-junction protein claudin-6 induces epithelial differentiation from mouse F9 and embryonic stem cells.

The tight-junction protein claudin-6 induces epithelial differentiation from mouse F9 and embryonic stem cells.
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DOI:
10.1371/journal.pone.0075106
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Chiba H
Chiba H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sugimoto K;Ichikawa-Tomikawa N;Satohisa S;Akashi Y;Kanai R;Saito T;Sawada N;Chiba H

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在上皮形成过程中,必须建立细胞粘附和极性以维持组织组装并分离体内的生物区室。然而,上皮形态发生的分子基础,特别是细胞粘附分子在干细胞分化为上皮细胞中的作用,仍然不清楚。在这里,我们表明,紧密连接蛋白,claudin-6(Cldn 6)的稳定和有条件的表达,触发小鼠F9干细胞的上皮形态发生。我们还证明Cldn 6诱导其他紧密连接和微绒毛分子的表达,包括Cldn 7,occludin,ZO-1α+和ezrin/radixin/moesin-binding phosphoprotein 50。通过使用RNA干扰或产气荚膜梭菌肠毒素的C-末端一半的Cldn 6的衰减来抑制这些事件。此外,在小鼠胚胎干细胞中也获得了类似的结果。因此,我们已经发现Cldn 6作为一种新的线索诱导上皮分化。
During epithelialization, cell adhesions and polarity must be established to maintain tissue assemblies and separate the biological compartments in the body. However, the molecular basis of epithelial morphogenesis, in particular, a role of cell adhesion molecules in epithelial differentiation from stem cells, remains unclear. Here, we show that the stable and conditional expression of a tight-junction protein, claudin-6 (Cldn6), triggers epithelial morphogenesis in mouse F9 stem cells. We also demonstrate that Cldn6 induces the expression of other tight-junction and microvillus molecules including Cldn7, occludin, ZO-1α+, and ezrin/radixin/moesin-binding phosphoprotein50. These events were inhibited by attenuation of Cldn6 using RNA interference or the C-terminal half of Clostridium Perfringens enterotoxin. Furthermore, similar results were obtained in mouse embryonic stem cells. Thus, we have uncovered that the Cldn6 functions as a novel cue to induce epithelial differentiation.
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