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.

中文翻译：

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通过单细胞 RNA 测序和空间转录组学的整合破译人类子宫腺肌病的综合转录图谱。


子宫腺肌症是一种人们知之甚少的妇科疾病，缺乏有效的治疗方法。关于“内陷”和“化生”理论的争议仍然存在。子宫内膜-子宫肌层连接处（EMJ）连接子宫内膜和子宫肌层，对于子宫腺肌症的诊断和分类具有重要意义，但对其的深入研究才刚刚开始。利用单细胞 RNA 测序和空间分析，我们绘制了在位子宫内膜、病变和 EMJ 的转录变化图。在病变内，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”发病机制理论之间复杂的相互作用。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显着差异，病变中涉及多效蛋白、TWEAK 和 WNT 级联的异常信号传导。这项研究揭示了子宫腺肌病病变内独特的干细胞样和侵袭性细胞亚群、功能失调的信号传导和 EMJ 异常，这对于制定精确的诊断和治疗策略至关重要。