Wnt10b-BMP6间的活化-抑制信号交流调控毛囊周期性再生的研究

项目名称： Wnt10b-BMP6间的活化-抑制信号交流调控毛囊周期性再生的研究

项目编号： No.81472895

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李玉红

作者单位： 中国人民解放军第三军医大学

项目金额： 75万元

中文摘要： 毛囊的周期性生长由毛囊干细胞（HFSC）介导。HFSC具有周期性活化与静息的特征，为成体干细胞和再生医学研究提供了一个很好的模型。本项目在青年基金研究率先发现Wnt10b能诱导毛囊周期性再生的基础上，对毛囊周期性再生的调控机制进行深入研究。本项目拟首先通过荧光双标、谱系示踪等方法证实毛囊周期性再生分别受到Wnt信号和BMP信号的正向和负向调控；在此基础上，培养毛囊、分离培养HFSC，通过腺病毒载体进行过表达实验、通过CRISPR/Cas9技术进行基因敲除实验，以分别从在体和离体两方面阐明HFSC静息与活化的调控机制：Wnt10b通过CyclinD正向调控CDK4，BMP6通过NFATc1负向调控CDK4，Wnt与BMP间的活化-抑制信号交流共同调控HFSC的静息与活化，从而调控毛囊的周期性再生。本研究不仅有助于深入理解毛囊周期性再生的机制，而且也可为脱发等毛囊再生障碍疾病研究提供基础。

中文关键词： 毛囊干细胞；Wnt信号通路；毛囊周期；BMP信号通路；毛发再生

英文摘要： Hair follicle stem cells (HFSCs) are periodically activated and resulted in the cyclic regeneration of hair follicles. This characteristic provides a nice model for research on adult stem cell and regeneration medicine. Based on the previous results include Wnt10b can induce hair follicle regeneration, this project will focus on the regulation mechanism of the cyclic regeneration of hair follicles. At first, this project will research on the positive regulation of Wnt signaling pathways and negative regulation of BMP signaling pathways on hair follicle regeneration, through injection of adenovirus, immunofluorence, lineage tracing analysis and other normal methods. Then this project will focus on the mechanism of the regulation of the activation and quiescence of HFSCs both in vitro and in vivo. We will culture both hair follicles and HFSCs, and overexpress genes with adenovirus or knockout genes with a new technique named CRISPR/Cas9. For confirmation and detection, Western blot or real-time PCR will be used. The hypothesis is that canonical Wnt signaling regulates CDK4 positively through CyclinD, while BMP signaling regulates CDK4 negatively through NFATc1. The interaction between Wnt and BMP signaling pathways regulates the periodically activation of HFSCs, thus mediates the cyclic regeneration of hair follicles. This project will not only illustrate the mechanism of hair follicle regeneration, but also provide basic theory for researches on the diseases related to hair follicle cycle such as hair loss. At the same time, this project can provide new clues for research on the mechanism of activation and quiescence of other adult stem cells.

英文关键词： hair follicle stem cells;Wnt signaling pathway;hair cycle;BMP signaling pathway;hair follicle regeneration