Decoding adenomyosis pathogenesis using an assembloid model

Yiliang Xu

doi:10.1007/s11427-025-2981-1

2025-08-28

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DOI：10.1007/s11427-025-2981-1

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腺肌病由于缺乏能够准确模拟月经周期中子宫内膜组织动力学的体外模型，仍然是研究中的挑战。为解决这一差距，我们建立了一种子宫内膜组装体模型，该模型能够忠实地模拟周期依赖性的子宫内膜反应，并捕获腺肌病的关键细胞和分子特征，包括异位病灶特异性的上皮和间质异质性。单细胞转录组学显示，在分泌样期，异位上皮细胞向管腔主导、腺体缺乏的转录谱转变。这一转变与异位间质的重组相关——具体表现为BMP4+间质细胞的丢失和CRYAB+IL15+间质细胞的积累，这损害了BMP介导的间质-上皮信号传导，同时增强了WNT的激活。此外，异位上皮和间质细胞表现出增强的免疫和血管生成活性。我们的组装体平台不仅为研究腺肌病发病机制提供了具有生理相关性的模型，还提示异常WNT信号通路可作为潜在的治疗靶点，为机制驱动的治疗策略提供了新的机会。

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Science China-Life Sciences

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