From the Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M University, Houston, Texas 77030-3303.
J Biol Chem. 2013 Oct 4;288(40):28952-61. doi: 10.1074/jbc.M113.506873. Epub 2013 Aug 26.
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.
牙上皮干细胞 (DESC) 巢中的上皮细胞源源不断地供应，使小鼠切牙在整个生命过程中持续生长。阐明这种无限生长潜力的细胞和分子机制对于牙齿再生治疗具有广泛的兴趣。成纤维细胞生长因子 (FGF) 信号对于小鼠切牙的发育和产前发育过程中颈环 (CL) 的维持是必不可少的。然而，DESC 中的 FGF 信号如何控制细胞的自我更新和分化还不是很清楚。本文报道 FGF 信号对于 CL 中以及 DESC 球体中的 DESCs 的自我更新和防止细胞分化是必需的。抑制 FGF 信号通路会降低 DESC 球体中细胞的增殖并增加细胞凋亡。抑制 FGFR 或其下游信号转导途径会减少 CL 中表达 Lgr5 的细胞，并促进 DESC 球体和 CL 中的细胞分化。此外，破坏 FGF 途径会促进 Wnt 信号转导，从而在体外和体内促进 DESCs 中 Lgr5 的表达。这项研究为理解 DESC 的稳态、扩增和分化是如何受到调控的提供了新的视角。
