Liu Song, Li Xiaoyan, Gu Zhiyue, Wu Jiayu, Jia Shuangzheng, Shi Jinghua, Dai Yi, Wu Yushi, Yan Hailan, Zhang Jing, You Yan, Xue Xiaowei, Liu Lulu, Lang Jinghe, Wang Xiaoyue, Leng Jinhua
Center for Bioinformatics, National Infrastructures for Translational Medicine, Institute of Clinical Medicine & Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
National Clinical Research Center for Obstetric & Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
Cell Genom. 2025 Jan 8;5(1):100737. doi: 10.1016/j.xgen.2024.100737.
Endometriosis is a chronic condition with limited therapeutic options. The molecular aberrations promoting ectopic attachment and interactions with the local microenvironment sustaining lesion growth have been unclear, prohibiting development of targeted therapies. Here, we performed single-cell and spatial transcriptomic profiling of ectopic lesions and eutopic endometrium in endometriosis. We found that ectopic endometrial stromal (EnS) cells retained cyclical gene expression patterns of their eutopic counterparts while exhibiting unique gene expression that contributes to the pathogenesis of endometriosis. We identified two distinct ovarian stromal cells (OSCs) localized at different zones of the lesion, showing differential gene expression profiles associated with fibrosis and inflammation, respectively. We also identified WNT5A upregulation and aberrant activation of non-canonical WNT signaling in endometrial stromal cells that may contribute to the lesion establishment, offering novel targets for therapeutic intervention. These data will enhance our understanding of the molecular mechanisms underlying endometriosis and paves the way for developing non-hormonal treatments.
子宫内膜异位症是一种治疗选择有限的慢性疾病。促进异位附着以及与维持病变生长的局部微环境相互作用的分子异常尚不清楚，这阻碍了靶向治疗的发展。在此，我们对子宫内膜异位症的异位病变和在位内膜进行了单细胞和空间转录组分析。我们发现，异位子宫内膜间质（EnS）细胞保留了其在位对应细胞的周期性基因表达模式，同时表现出有助于子宫内膜异位症发病机制的独特基因表达。我们鉴定出两种不同的卵巢间质细胞（OSC），它们位于病变的不同区域，分别显示出与纤维化和炎症相关的差异基因表达谱。我们还发现WNT5A上调以及子宫内膜间质细胞中非经典WNT信号的异常激活，这可能有助于病变的形成，为治疗干预提供了新的靶点。这些数据将加深我们对子宫内膜异位症潜在分子机制的理解，并为开发非激素治疗方法铺平道路。
