去分化是指已分化的细胞，逆转成其早期干细胞的过程。临床中我们发现有些病例在角膜缘干细胞（LSCs）完全缺失后，中央的孤岛状角膜上皮体细胞（CECs）仍可长期维持稳定，甚至可在小片状损伤后再生修复。进而我们把小鼠EGFP+的中央CECs移植给完全去除角膜上皮组织的野生型小鼠，发现LSCs相关基因ADCG2和integrin α9可在该移植CECs高表达。据此，我们提出LSCs损伤时其抑制去分化的信号会减弱或消失，CECs的去分化进程会启动的新假设。本课题首先制备多种转基因小鼠模型，采用细胞谱系追踪等技术，意在精确验证与呼吸道粘膜上皮类似，CECs亦存在去分化现象，并对LSCs及CECs相关的“在体”微环境改变导致的这种去分化的生物学特性进行研究。研究结果有望解释新近多篇报道提出的LSCs地位的不明确性问题，并为发现新的CECs再生源奠定理论基础。

Dedifferentiation is a cellular process in which a partially or terminally differentiated cells reverts to there earlier adult stem cells. Clinically, we found that, in some total limbal stem cell deficiency cases, the central island corneal epithelial somatic cells (CECs) could keep self-stable and even self-healing after pieces of detachment. Further, we transplanted the EGFP+ mice's CECs to the corneal stroma of wild type mice after the whole corneal epithelium were debrided, and found that the LSCs related genes: ADCG2 and integrinα9 could over expressed in the transplanted CECs. Based on this previous work, we put forward a new hypothesis: The inhibition signal of LSCs will decrease or vanish after impairment or debridement, followed by the activation of CECs' dedifferentiation. In this project, we will first establish 8 transgenic mice models, using cellular linage tracing technique, intended to precisely testify, such as the respiratory tract epithelium, the phenomenon of dedifferentiation is also exist in the CECs. Further, Some biological characteristics of this phenomenon related to in vivo LSCs and CECs micro-environment changes will be studied. The ability of dedifferentiation in different location and different layers of CECs will also be evaluated. Hopefully, the results of this study will explain some uncertainty questions appeared in recent published papers, and should provide a theoretical foundation for the finding of new CECs sources.