Department of Obstetrics and Gynecology, Affiliated Women and Children Hospital of Jiaxing University, Jiaxing 314000, China.
Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Protein Cell. 2024 Jul 1;15(7):530-546. doi: 10.1093/procel/pwae012.
Adenomyosis is a poorly understood gynecological disorder lacking effective treatments. Controversy persists regarding "invagination" and "metaplasia" theories. The endometrial-myometrial junction (EMJ) connects the endometrium and myometrium and is important for diagnosing and classifying adenomyosis, but its in-depth study is just beginning. Using single-cell RNA sequencing and spatial profiling, we mapped transcriptional alterations across eutopic endometrium, lesions, and EMJ. Within lesions, we identified unique epithelial (LGR5+) and invasive stromal (PKIB+) subpopulations, along with WFDC1+ progenitor cells, supporting a complex interplay between "invagination" and "metaplasia" theories of pathogenesis. Further, we observed endothelial cell heterogeneity and abnormal angiogenic signaling involving vascular endothelial growth factor and angiopoietin pathways. Cell-cell communication differed markedly between ectopic and eutopic endometrium, with aberrant signaling in lesions involving pleiotrophin, TWEAK, and WNT cascades. This study reveals unique stem cell-like and invasive cell subpopulations within adenomyosis lesions identified, dysfunctional signaling, and EMJ abnormalities critical to developing precise diagnostic and therapeutic strategies.
子宫腺肌病是一种发病机制尚不完全清楚的妇科疾病，缺乏有效的治疗方法。“内陷”和“化生”理论仍存在争议。子宫内膜-子宫肌层交界处（EMJ）连接子宫内膜和子宫肌层，对于诊断和分类子宫腺肌病很重要，但对其的深入研究才刚刚开始。我们使用单细胞 RNA 测序和空间分析技术，绘制了在位子宫内膜、病变和 EMJ 的转录变化图谱。在病变中，我们鉴定了独特的上皮（LGR5+）和侵袭性基质（PKIB+）亚群，以及 WFDC1+祖细胞，支持“内陷”和“化生”发病机制理论之间的复杂相互作用。此外，我们观察到内皮细胞异质性和涉及血管内皮生长因子和血管生成素途径的异常血管生成信号。异位和在位子宫内膜之间的细胞间通讯存在明显差异，病变中涉及的异常信号包括外泌体、TWEAK 和 WNT 级联。这项研究揭示了在子宫腺肌病病变中鉴定出的独特的干细胞样和侵袭性细胞亚群、功能失调的信号以及 EMJ 异常，这些对于开发精确的诊断和治疗策略至关重要。
