c-Fos在皮肤上皮干细胞衰老中的作用研究

富含干细胞的皮肤上皮组织具有人体中最直观的衰老表型，为组织干细胞的衰老研究提供了理想模型。我们通过深入挖掘现有的临床数据，发现c-Fos的表达水平与人皮肤上皮干细胞的衰老过程可能密切相关，并在小鼠皮肤干细胞培养中进行了初步功能验证。因此，我们首次提出“c-Fos调控皮肤上皮干细胞衰老”这一科学假说。同时，我们前期还建立了一整套在小鼠体内快速构建转基因皮肤模型和快速模拟人皮肤衰老表型的创新技术体系，突破了皮肤衰老研究的关键技术瓶颈。在这些前期基础上，我们将在本项目中利用小鼠模型来探讨c-Fos在体内皮肤上皮干细胞衰老过程中的功能与作用机制。具体而言，我们将制备条件性过表达/敲低/敲除 c-Fos的体内皮肤上皮模型，解析其在衰老过程中的表型与转录组变化，并在此基础上鉴定c-Fos调控体内皮肤上皮干细胞衰老的主要靶基因。本研究将揭示皮肤上皮干细胞衰老的新分子机制，为新型皮肤抗衰老技术奠定基础。

Somatic stem cells are the basis for the homeostasis and wound repair of most adult tissues. Elucidating their aging mechanisms is of great importance for our understanding of human aging process. The stem cell enriched skin epithelium has the most obviously aging phenotypes in human body, providing an idea system for adult stem cell aging studies. Through in-depth analysis of existing clinical data, we found a significant correlation between the expression level of transcription factor c-Fos and the aging process of human skin epithelial stem cells. Our preliminary data also implicated a functional importance of c-Fos in mouse skin epidermal stem cells. Therefore, we proposed a novel hypothesis that c-Fos may regulate the aging process of skin epidermal stem cells. Meanwhile, we have also established a set of innovative technique for rapidly constructing genetically modified skin models and preparing skin aging models in mice, breaking through the key technical bottlenecks in skin aging research. Based on these, we will use mouse models to elucidating the role and functional mechanisms of c-Fos in regulating the aging process of skin epithelium . Specifically, we will construct conditional c-Fos overexpression/knock-down/knockout in vivo skin models; characterize phenotypic and transcriptome changes in their aging process; and using them to identify main target genes of c-Fos in regulating skin epithelial stem cell aging. Our research will give us novel insights into the aging mechanisms of skin epithlial stem cells, and will provide us an important foundation for the development of novel skin anti-aging therapies.