Fibroblast Growth Factor Signaling Is Essential for Self-renewal of Dental Epithelial Stem Cells
Fibroblast Growth Factor Signaling Is Essential for Self-renewal of Dental Epithelial Stem Cells
复制标题
成纤维细胞生长因子信号传导对于牙上皮干细胞的自我更新至关重要
DOI：
10.1074/jbc.m113.506873
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发表时间：
2013-10-04
影响因子：
4.8
通讯作者：
Wang, Fen
中科院分区：
文献类型：
--
作者：
Chang, Julia Yu Fong;Wang, Cong;Wang, Fen
来自宫颈环（CL）中的牙上皮干细胞（DESC）龛的上皮细胞的恒定供应使小鼠切牙能够在整个生命中持续生长。阐明这种无限生长潜力背后的细胞和分子机制对于牙齿再生疗法具有广泛的意义。成纤维细胞生长因子（FGF）信号传导对于小鼠切牙的发育和产前发育期间CL的维持是必不可少的。然而，在DESCs中FGF信号传导如何控制细胞的自我更新和分化还不清楚。在此，我们报告说，FGF信号是必不可少的自我更新和防止细胞分化的DESC在CL以及在DESC领域。抑制FGF信号通路降低了DESC球中细胞的增殖并增加了细胞凋亡。抑制FGFR或其下游信号转导途径减少了CL中的Lgr 5表达细胞，并促进了DESC球和CL中的细胞分化。此外，FGF途径的破坏废除了Wnt信号传导，以促进体外和体内DESC中Lgr5的表达。这项研究为理解DESCs的稳态、扩增和分化的调控机制提供了新的思路。
A constant supply of epithelial cells from dental epithelial stem cell (DESC) niches in the cervical loop (CL) enables mouse incisors to grow continuously throughout life. Elucidation of the cellular and molecular mechanisms underlying this unlimited growth potential is of broad interest for tooth regenerative therapies. Fibroblast growth factor (FGF) signaling is essential for the development of mouse incisors and for maintenance of the CL during prenatal development. However, how FGF signaling in DESCs controls the self-renewal and differentiation of the cells is not well understood. Herein, we report that FGF signaling is essential for self-renewal and the prevention of cell differentiation of DESCs in the CL as well as in DESC spheres. Inhibiting the FGF signaling pathway decreased proliferation and increased apoptosis of the cells in DESC spheres. Suppressing FGFR or its downstream signal transduction pathways diminished Lgr5-expressing cells in the CL and promoted cell differentiation both in DESC spheres and the CL. Furthermore, disruption of the FGF pathway abrogated Wnt signaling to promote Lgr5 expression in DESCs both in vitro and in vivo. This study sheds new light on understanding the mechanism by which the homeostasis, expansion, and differentiation of DESCs are regulated.