p16INK4a-pRb通路及其相关表观遗传调控在人真皮干细胞自我更新与衰老中的作用

项目名称： p16INK4a-pRb通路及其相关表观遗传调控在人真皮干细胞自我更新与衰老中的作用

项目编号： No.31201099

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 发育生物学与生殖生物学

项目作者： 刘爽

作者单位： 中国科学院动物研究所

项目金额： 26万元

中文摘要： 皮肤来源前体细胞（SKPs）是一类具有真皮干细胞特性的多潜能细胞，在皮肤正常生理功能维持与损伤修复中发挥关键作用,对于皮肤创伤修复和组织工程皮肤的构建具有重要意义。但人们对SKPs的自我更新缺乏研究，SKPs在体外无法大量扩增，给SKPs的深入研究和应用造成极大障碍。本实验室在前期工作中首次发现人SKPs离开其体内微环境后将迅速发生细胞衰老现象，前期结果提示p16INK4a-pRb通路可能在其中发挥关键作用。本课题将在前期发现的基础上，进一步详细研究p16INK4-pRb信号通路在SKPs体内外衰老调控中的具体作用，深入挖掘染色质修饰因子PcG蛋白参与p16INK4a表达和活性调节以及真皮干细胞衰老调控的具体机制，并探索其与皮肤衰老的联系。我们的研究将有助于全面了解真皮干细胞的调控机制，对认识和对抗皮肤衰老具有积极意义，对发展真皮干细胞应用于皮肤组织工程与再生医学治疗也将起到推动作用。

中文关键词： 成体干细胞；自我更新；细胞衰老；水凝胶支架；移植

英文摘要： Skin-derived precursors (SKPs) are multipotent progenitor cells with properties of dermal stem cells. SKPs play important roles in the homeostasis and wound repair of human skin, which make them promising in skin tissue engineering. Besides, their ability to differentiate into a broad panel of cell types endows them with the therapeutic potential even in other tissues. However, in-vitro expansion of SKPs is defective and people so far know very little about their self-renewal regulation, which definitely hampers their application in regenerative medicine. Our previous work showed that after separation from their physiological microenvironment, human foreskin-derived SKPs quickly senesced and lost their self-renewal ability, which resulted in the failure of their long-term expansion.Our results also imply that p16INK4a pathway may play a critical role in this process. Based on this discovery, the present study is to investigate in detail the role of p16INK4a pathway in SKP senescence and aging regulation, both in vitro and in vivo. We also propose to explore the functions and regulation mechanisms of p16INK4a related PcG proteins in SKP self-renewal and aging. Our study will not only promote the practice of SKPs in medicine, but also help people learn more about skin aging in order to fight against it.

英文关键词： adult stem cells；self-renewal；cellular senescence；hydrogel scaffold；transplantation