Localization of putative stem cells in dental epithelium and their association with Notch and FGF signaling.
Localization of putative stem cells in dental epithelium and their association with Notch and FGF signaling.
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DOI：
10.1083/jcb.147.1.105
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发表时间：
1999-10-04
影响因子：
7.8
通讯作者：
Thesleff, I
中科院分区：
文献类型：
--
作者：
Harada, H;Kettunen, P;Jung, H S;Mustonen, T;Wang, Y A;Thesleff, I
持续生长的小鼠切牙是分析干细胞谱系机制的理想模型。我们设计了一种用于切牙根尖的器官培养方法，并通过5-溴-2 ′-脱氧尿苷和DiI标记来分析上皮细胞谱系。我们的研究结果表明，干细胞存在于宫颈环上皮中，该上皮由星状网状细胞的中央核心组成，周围环绕着一层基底上皮细胞，并且它们会产生过渡放大后代，分化为形成釉的成釉细胞。我们确定了缓慢分裂的细胞之间的Notch 1表达星状网状细胞在特定位置附近的基底上皮细胞表达lunatic边缘，一种分泌分子调节Notch信号。从组织重组研究中已知，在小鼠切牙中，间充质调节上皮的连续生长。Fgf-3和Fgf-10的表达仅限于基底上皮细胞和表达其受体Fgfr 1b和Fgfr 2b的过渡放大细胞下面的间充质。当FGF-10蛋白与珠粒一起应用于培养的宫颈袢上皮时，其刺激细胞增殖以及Lunatic Fringe的表达。我们提出了一个模型，其中FGF信号从间充质调节Notch途径在牙齿上皮干细胞通过刺激的lunatic边缘表达，从而在耦合的有丝分裂和干细胞的命运决定的核心作用。
The continuously growing mouse incisor is an excellent model to analyze the mechanisms for stem cell lineage. We designed an organ culture method for the apical end of the incisor and analyzed the epithelial cell lineage by 5-bromo-2′-deoxyuridine and DiI labeling. Our results indicate that stem cells reside in the cervical loop epithelium consisting of a central core of stellate reticulum cells surrounded by a layer of basal epithelial cells, and that they give rise to transit-amplifying progeny differentiating into enamel forming ameloblasts. We identified slowly dividing cells among the Notch1-expressing stellate reticulum cells in specific locations near the basal epithelial cells expressing lunatic fringe, a secretory molecule modulating Notch signaling. It is known from tissue recombination studies that in the mouse incisor the mesenchyme regulates the continuous growth of epithelium. Expression of Fgf-3 and Fgf-10 were restricted to the mesenchyme underlying the basal epithelial cells and the transit-amplifying cells expressing their receptors Fgfr1b and Fgfr2b. When FGF-10 protein was applied with beads on the cultured cervical loop epithelium it stimulated cell proliferation as well as expression of lunatic fringe. We present a model in which FGF signaling from the mesenchyme regulates the Notch pathway in dental epithelial stem cells via stimulation of lunatic fringe expression and, thereby, has a central role in coupling the mitogenesis and fate decision of stem cells.