miR-31/p21相关信号通路调控角膜缘干细胞生物学特性的的机制研究

The fate of the adult stem cells is closely related with its surrounding microenvironment. To explore the essence of the maintenance of the functional properties of limbal stem cells(LSCs),we have designed the ES microenvironment culture system. In our previous studies, we have found that corneal epithelial cells could be dedifferentiated and retained the undifferentiated phenotype in ES microenvironment. Furthermore, this culture system could maintain the stemness of LSCs via telomerase-p21-mitochondria axis and the activation of FAK/Wnt signaling pathways.Studies have shown that microRNAs could regulate the functional properties of adult stem cells. Based on our previous work, we propose to confirm and consummate the mechanisms of ES microenvironment regulating the functional properties of LSCs : 1. To verify the activation of miR-31/FIH-1/p21 signaling pathway plays vital roles in the maintenance of functional properties of LSCs and the regulation of its apoptosis; 2. To confirm the roles of p21/Survivin in LSCs; 3. To figure out the mechanisms of miR-31 in maintenance the functional properties of LSCs. This project will focus on the scientific problem "the essence of ES microenvironment", aim to disclose the mechanisms of ES microenvironment maintenance the functional properties of adult LSCs based on the regulation of the microRNAs, and to provide novel scientific strategies and research platform for ocular surface resconstruction.

成体干细胞的命运与其生存的微环境密切相关。为探讨角膜缘干细胞(limbal stem cells,LSCs)功能特性维持的本质，我们设计了胚胎干细胞(Embryonic Stem Cells,ES)微环境培养体系，发现其可以使角膜上皮细胞去分化，并且能够通过端粒酶-p21-线粒体通路以及FAK/Wnt信号通路的激活维持LSCs的干性。研究表明，microRNAs具有调控成体干细胞生物学特性的功能。结合前期的工作积累，本项目拟进一步：1.证明miR-31/FIH-1/p21信号通路的活化参与LSCs干性维持与凋亡的调控；2. 明确p21/Survivin的作用；3.揭示miR-31维持LSCs功能的机制。本项目紧紧围绕"ES微环境作用的本质"这一科学问题，从microRNAs调控机制入手，旨在阐明ES微环境调控LSCs功能的机制,为眼表重建提供新的策略与研究平台。