Runx1-Stat3 signaling regulates the epithelial stem cells in continuously growing incisors.
Runx1-Stat3 signaling regulates the epithelial stem cells in continuously growing incisors.
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DOI：
10.1038/s41598-018-29317-6
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发表时间：
2018-07-19
影响因子：
4.6
通讯作者：
Yamashiro T
中科院分区：
文献类型：
--
作者：
Sarper SE;Inubushi T;Kurosaka H;Ono Minagi H;Kuremoto KI;Sakai T;Taniuchi I;Yamashiro T
啮齿动物的门牙永久生长，牙釉质生成的稳态通过来自宫颈环中假定的干细胞的上皮祖细胞的持续供应来维持。我们在此报告，Runx1 调节表达 Lgr5 的上皮干细胞及其随后持续分化为成釉细胞。上皮 Runx1 缺陷的小鼠表现出门牙显着缩短、颈环发育不全和牙釉质缺陷。在这种突变的宫颈环中，牙上皮的增殖受到显着干扰，Lgr5和牙釉质基质蛋白的表达显着下调。有趣的是，Socs3（一种 Stat3 信号传导抑制剂）的表达上调，并且 Stat3 磷酸化在突变的宫颈环中被特异性抑制。体外药物 Stat3 抑制会干扰野生型切牙细菌中 Lgr5 和牙釉质基质蛋白的表达。相反，Stat3 的药物激活可以挽救 Runx1 突变体的缺陷表型，该突变体具有上调的 Lgr5 和牙釉质基质蛋白基因。目前的结果提供了 Runx1 在调节表达 Lgr5 的上皮干细胞和发育中的门牙中成釉细胞祖细胞的分化中的作用的第一个证据。我们的研究还表明 Stat3 调节颈环中的 Runx1-Lgr5 轴。
Rodent incisors grow permanently and the homeostasis of enamel production is maintained by a continuous supply of epithelial progenitors from putative stem cells in the cervical loop. We herein report that Runx1 regulates the Lgr5-expressing epithelial stem cells and their subsequent continuous differentiation into ameloblasts. Mice deficient in epithelial Runx1 demonstrate remarkable shortening of the incisors with underdevelopment of the cervical loop and enamel defects. In this mutant cervical loop, the proliferation of the dental epithelium was significantly disturbed and the expression of Lgr5 and enamel matrix proteins was remarkably downregulated. Interestingly, the expression of Socs3, an inhibitor of Stat3 signaling, was upregulated and Stat3 phosphorylation was suppressed specifically in the mutant cervical loop. The expression of Lgr5 and the enamel matrix protein in the wild-type incisor germs is disturbed by pharmaceutical Stat3 inhibition in vitro., of. Conversely, pharmaceutical activation of Stat3 rescues the defective phenotypes of the Runx1 mutant with upregulated Lgr5 and enamel matrix protein genes. The present results provide the first evidence of the role of Runx1 regulates the Lgr5-expressing epithelial stem cells and differentiation of ameloblast progenitors in the developing incisors. Our study also demonstrates that Stat3 modulates the Runx1-Lgr5 axis in the cervical loop.
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影响因子：
3.7
作者：
Ono Minagi H;Sarper SE;Kurosaka H;Kuremoto KI;Taniuchi I;Sakai T;Yamashiro T
通讯作者：
Yamashiro T
影响因子：
2.9
作者：
Gurbuz V;Konac E;Varol N;Yilmaz A;Gurocak S;Menevse S;Sozen S
通讯作者：
Sozen S
影响因子：
3.7
作者：
Hu J;Yang Z;Wang J;Yu J;Guo J;Liu S;Qian C;Song L;Wu Y;Cheng J
通讯作者：
Cheng J
影响因子：
2.6
作者：
Raveh, Eli;Cohen, Shulamit;Gat, Uri
通讯作者：
Gat, Uri
影响因子：
4.4
作者：
LEVANON, D;NEGREANU, V;GRONER, Y
通讯作者：
GRONER, Y