CXCR4/CXCL12 signaling impacts enamel progenitor cell proliferation and motility in the dental stem cell niche.
CXCR4/CXCL12 signaling impacts enamel progenitor cell proliferation and motility in the dental stem cell niche.
复制标题
DOI：
10.1007/s00441-015-2248-y
复制
发表时间：
2015-12
影响因子：
3.6
通讯作者：
Harley BA
中科院分区：
文献类型：
--
作者：
Yokohama-Tamaki T;Otsu K;Harada H;Shibata S;Obara N;Irie K;Taniguchi A;Nagasawa T;Aoki K;Caliari SR;Weisgerber DW;Harley BA
牙齿干细胞位于啮齿动物门牙的近端。这些干细胞驻留在牙齿上皮干细胞龛中，称为顶芽。我们专注于识别利基中趋化信号的关键特征。在这里，我们报告说，CXCR 4/CXCL 12信号影响釉质祖细胞的增殖和运动在牙齿干细胞龛细胞。我们报告细胞在顶芽表达CXCR 4 mRNA在高水平，而表达限制在基底上皮（BE）和过渡放大（TA）细胞区域。此外，CXCL 12配体存在于邻近顶芽的间充质细胞中。然后，我们进行了功能获得和丧失分析，以更好地阐明CXCR 4和CXCL 12的作用。CXCR 4缺陷小鼠含有上皮细胞聚集体，而突变切牙中的细胞增殖也显著减少。我们证明，在体外，牙齿上皮细胞向来源的CXCL 12迁移，而敲低CXCR 4受损的运动，并导致形成致密的细胞集落。这些结果表明，CXCR 4的表达可能是至关重要的激活釉祖细胞分裂和CXCR 4/CXCL 12信号可以控制运动的上皮祖细胞从牙齿干细胞龛。
Dental stem cells are located at the proximal ends of rodent incisors. These stem cells reside in the dental epithelial stem cell niche, termed the apical bud. We focused on identifying critical features of a chemotactic signal in the niche. Here, we report that CXCR4/CXCL12 signaling impacts enamel progenitor cell proliferation and motility in dental stem cell niche cells. We report cells in the apical bud express CXCR4 mRNA at high levels while expression is restricted in the basal epithelium (BE) and transit-amplifying (TA) cell regions. Furthermore, the CXCL12 ligand is present in mesenchymal cells adjacent to the apical bud. We then performed gain- and loss-of-function analyses to better elucidate the role of CXCR4 and CXCL12. CXCR4-deficient mice contain epithelial cell aggregates, while cell proliferation in mutant incisors was also significantly reduced. We demonstrate in vitro that dental epithelial cells migrate toward sources of CXCL12, whereas knocking down CXCR4 impaired motility and resulted in formation of dense cell colonies. These results suggest that CXCR4 expression may be critical for activation of enamel progenitor cell division and that CXCR4/CXCL12 signaling may control movement of epithelial progenitors from the dental stem cell niche.