Runx1-Stat3 signaling regulates the epithelial stem cells in continuously growing incisors

Abstract 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 contin...

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Autores principales:	Safiye E. Sarper, Toshihiro Inubushi, Hiroshi Kurosaka, Hitomi Ono Minagi, Koh-ichi Kuremoto, Takayoshi Sakai, Ichiro Taniuchi, Takashi Yamashiro
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/63ae1d58056c49849a85d69800a0577e
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spelling	oai:doaj.org-article:63ae1d58056c49849a85d69800a0577e2021-12-02T15:08:41ZRunx1-Stat3 signaling regulates the epithelial stem cells in continuously growing incisors10.1038/s41598-018-29317-62045-2322https://doaj.org/article/63ae1d58056c49849a85d69800a0577e2018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29317-6https://doaj.org/toc/2045-2322Abstract 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.Safiye E. SarperToshihiro InubushiHiroshi KurosakaHitomi Ono MinagiKoh-ichi KuremotoTakayoshi SakaiIchiro TaniuchiTakashi YamashiroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Safiye E. Sarper Toshihiro Inubushi Hiroshi Kurosaka Hitomi Ono Minagi Koh-ichi Kuremoto Takayoshi Sakai Ichiro Taniuchi Takashi Yamashiro Runx1-Stat3 signaling regulates the epithelial stem cells in continuously growing incisors
description	Abstract 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.
format	article
author	Safiye E. Sarper Toshihiro Inubushi Hiroshi Kurosaka Hitomi Ono Minagi Koh-ichi Kuremoto Takayoshi Sakai Ichiro Taniuchi Takashi Yamashiro
author_facet	Safiye E. Sarper Toshihiro Inubushi Hiroshi Kurosaka Hitomi Ono Minagi Koh-ichi Kuremoto Takayoshi Sakai Ichiro Taniuchi Takashi Yamashiro
author_sort	Safiye E. Sarper
title	Runx1-Stat3 signaling regulates the epithelial stem cells in continuously growing incisors
title_short	Runx1-Stat3 signaling regulates the epithelial stem cells in continuously growing incisors
title_full	Runx1-Stat3 signaling regulates the epithelial stem cells in continuously growing incisors
title_fullStr	Runx1-Stat3 signaling regulates the epithelial stem cells in continuously growing incisors
title_full_unstemmed	Runx1-Stat3 signaling regulates the epithelial stem cells in continuously growing incisors
title_sort	runx1-stat3 signaling regulates the epithelial stem cells in continuously growing incisors
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/63ae1d58056c49849a85d69800a0577e
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Runx1-Stat3 signaling regulates the epithelial stem cells in continuously growing incisors

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