晶状体再生修复过程中JAM-C对上皮干细胞分化和纤维细胞有序排列的调控机制

婴幼儿白内障是儿童主要致盲眼病，目前治疗效果欠佳。本课题组通过微创新术式实现功能性晶状体原位再生（Nature 2016），然而目前该技术存在上皮干细胞分化能力不足和纤维细胞不能长期有序排列的瓶颈。我们前期利用蛋白质组学技术，发现再生晶状体和正常晶状体中JAM-C的表达存在显著差异。在对JAM-C基因敲除小鼠动物模型的研究中，我们发现晶状体上皮干细胞不能正常分化，纤维细胞排列紊乱；通过转录组测序发现差异基因富集于MAPK和Wnt通路。这些结果提示JAM-C可能通过影响bFGF-MAPK/ERK和Wnt-JNK通路调控晶状体上皮干细胞分化和纤维细胞有序排列。本项目拟进一步利用JAM-C基因敲除小鼠，大鼠晶状体外植体系统、兔晶状体再生模型，深入探讨在晶状体再生过程中JAM-C对上皮干细胞分化和纤维细胞有序排列的调控机制，为进一步优化再生晶状体的结构和功能提供理论基础。

Pediatric cataract is the major cause of blindness in children; however, the current surgical outcome is not satisfactory. Our group achieved functional in situ lens regeneration by minimally invasive surgery (nature 2016). At present, the core problem of this treatment is how to further improve the differentiation ability of epithelial stem cells and maintain the orderly alignment of lens fibers. Recently, we found that there was a significant difference in JAM-C expression between in situ regenerated lens and normal lens by proteomics analysis. In JAM-C-/- mice, we found lens epithelial stem cells poorly differentiated and lens fibers were disorderly aligned; By high-throughput RNA sequencing, we found differentially expressed genes of JAM-C-/- mice were characteristically enriched in MAPK and Wnt signal transduction pathways. These results indicated that JAM-C may regulate differentiation of epithelial stem cells and the orderly alignment of fiber cells through bFGF-MAPK/ERK and Wnt-JNK signaling pathways. This project aims to further explore the regulatory mechanism of JAM-C on the differentiation of epithelial stem cells and the orderly alignment of fiber cells during lens regeneration using JAM-C-/- mice, rat lens epithelial explant and rabbit lens regeneration model following minimally invasive surgery, so as to provide a theoretical basis for further optimizing the structure and function of regenerated lens.