血液中循环子宫内膜细胞（CECs）在子宫内膜异位症发病机制中的研究

子宫内膜异位症（EM）发病机制尚不明确，经血逆流和血行种植等多种学说均不能完全解释EM的发生。我们前期研究发现EM患者外周血中存在循环内膜细胞，可能与EM的发病密切相关，提出了“循环子宫内膜细胞假说”。本项目拟采用差相富集、免疫荧光和单细胞显微操作等方法，捕获EM患者外周血中的循环内膜细胞；制备在位内膜、异位内膜单细胞悬液并纯化，分别获取单个细胞。通过基因组、甲基化组及转录组测序，在单细胞分子层面进行研究，鉴定在位、循环中、异位内膜细胞的亚群，揭示三者间的进化关系，确定发病机制中的关键细胞。分别建立裸鼠子宫内膜损伤模型和经血逆流模型，观察EGFP标记的EM患者在位内膜细胞在两种裸鼠模型中的成像轨迹及病灶形成过程，验证我们提出的假说。拓展完善内异症发病机制，寻找EM生物标志物。

The pathogenesis of endometriosis (EM) is still unclear. The current theories such as retrograde menstruation and blood transplantation could not fully explain the cause of EM. We previously found that circulating endometrial cells in the peripheral blood of EM patients may be closely related to the pathogenesis of EM, and proposed "circulating endometrial cell hypothesis." This study aims to capture circulating endometrial cells in the peripheral blood of EM patients using subtraction enrichment, immunofluorescence and single cell micromanipulation, to prepare single cell suspension of eutopic endometrial and ectopic endometrial and purify them separately to obtain respective single cell. Through genomic, methylation and transcriptome sequencing, single-cell molecular level studies were performed to identify subpopulations of eutopic, ectopic and circulating endometrial cells, and finally to reveal the evolutionary relationships and identify the key cells in the pathogenesis of EM. To verify the hypothesis, we also will establish the nude mice models with endometrial injury and the models imitating retrograde menstruation using EGFP-labeled eutopic endometrial cells to visually observe the trajectory of cells and the formation of lesions . This study contributes to reveal the pathogenesis of EM and search for EM biomarkers.