Department of Orofacial Sciences and Program in Craniofacial and Mesenchymal Biology, UCSF, USA.
Dev Biol. 2012 Jun 15;366(2):357-66. doi: 10.1016/j.ydbio.2012.03.012. Epub 2012 Apr 18.
Stem cells are essential for the regeneration and homeostasis of many organs, such as tooth, hair, skin, and intestine. Although human tooth regeneration is limited, a number of animals have evolved continuously growing teeth that provide models of stem cell-based organ renewal. A well-studied model is the mouse incisor, which contains dental epithelial stem cells in structures known as cervical loops. These stem cells produce progeny that proliferate and migrate along the proximo-distal axis of the incisor and differentiate into enamel-forming ameloblasts. Here, we studied the role of E-cadherin in behavior of the stem cells and their progeny. Levels of E-cadherin are highly dynamic in the incisor, such that E-cadherin is expressed in the stem cells, downregulated in the transit-amplifying cells, re-expressed in the pre-ameloblasts and then downregulated again in the ameloblasts. Conditional inactivation of E-cadherin in the cervical loop led to decreased numbers of label-retaining stem cells, increased proliferation, and decreased cell migration in the mouse incisor. Using both genetic and pharmacological approaches, we showed that Fibroblast Growth Factors regulate E-cadherin expression, cell proliferation and migration in the incisor. Together, our data indicate that E-cadherin is an important regulator of stem cells and their progeny during growth of the mouse incisor.
干细胞对于许多器官的再生和稳态至关重要，如牙齿、毛发、皮肤和肠道。尽管人类牙齿的再生能力有限，但许多动物已经进化出了不断生长的牙齿，为基于干细胞的器官更新提供了模型。一个研究得很好的模型是小鼠的切牙，它含有被称为颈环的结构中的牙上皮干细胞。这些干细胞产生的后代在切牙的近-远轴上增殖和迁移，并分化为形成釉质的成釉细胞。在这里，我们研究了 E-钙黏蛋白在干细胞及其后代行为中的作用。E-钙黏蛋白在切牙中的水平是高度动态的，因此 E-钙黏蛋白在干细胞中表达，在过渡扩增细胞中下调，在前成釉细胞中重新表达，然后在成釉细胞中再次下调。在颈环中条件性失活 E-钙黏蛋白导致标记保留的干细胞数量减少、增殖增加和细胞迁移减少在小鼠切牙中。通过遗传和药理学方法，我们表明成纤维细胞生长因子调节 E-钙黏蛋白的表达、细胞增殖和迁移在切牙中。总之，我们的数据表明，E-钙黏蛋白是小鼠切牙生长过程中干细胞及其后代的重要调节因子。
