Intrauterine adhesions (IUA), characterized by endometrial fibrosis, pose a serious threat to women's reproductive health, yet their molecular mechanisms remain poorly understood. Here, we use single-cell RNA sequencing (scRNA-seq) to profile 139,395 single cells from nine individuals in the proliferative phase. We identify seven stromal and five macrophage subsets, revealing increased immune cell infiltration and a profibrotic shift in macrophage states. Immunohistochemistry confirms elevated CD68+ macrophages and higher expression of S100A8, CCL2, CCL5, and SPP1 in IUA tissues. In vitro, macrophage-derived CCL5 and SPP1 promote fibroblast-to-myofibroblast transition. Trajectory and ligand-receptor analysis highlight profibrotic macrophage lineages and TGF-beta signaling as a key driver of fibrosis. Integration with secretory-phase single-cell data provides a comprehensive view of IUA across menstrual phases. These findings uncover a pivotal role for macrophage-stromal interactions in IUA progression and suggest potential therapeutic targets.
基金:
Yunnan Fundamental Research Projects (Grant No. 202201AU070232), Yunnan Fundamental Research Projects (Grant No. 202501AT070168), the Scientific Research Fund of the Yunnan Provincial Department of Education (Grant No. 2022J0060), the Talent Training Fund [32130034, 82192874]; National Natural Science Foundation of China [2022YFA1103100]; National Key Research and Development Program of China [202102AA100007]; Major Basic Research Project of Natural Science Foundation of Yunnan Province [202501AT070168]; Yunnan Fundamental Research Projects [2022J0060]; Scientific Research Fund of the Yunnan Provincial Department of Education [KKZ3202473060]; Talent Training Fund of Kunming University of Science and Technology [202401AY070001-121]; Yunnan Provincial Basic Research Program Kunming Medical University Joint Special Project
第一作者机构:[1]Kunming Univ Sci & Technol, Inst Primate Translat Med, State Key Lab Primate Biomed Res, Kunming, Peoples R China[2]Yunnan Key Lab Primate Biomed Res, Kunming, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Kunming Univ Sci & Technol, Inst Primate Translat Med, State Key Lab Primate Biomed Res, Kunming, Peoples R China[2]Yunnan Key Lab Primate Biomed Res, Kunming, Peoples R China
推荐引用方式(GB/T 7714):
Dong E.,Zhou Zhengli,Chen Tingwei,et al.Single-cell sequencing uncovers disrupted stromal-macrophage communication as a driver of intrauterine adhesion progression[J].COMMUNICATIONS BIOLOGY.2025,8(1):doi:10.1038/s42003-025-08634-3.
APA:
Dong, E.,Zhou, Zhengli,Chen, Tingwei,Zhang, Bo,Yin, Yu...&Li, Tianqing.(2025).Single-cell sequencing uncovers disrupted stromal-macrophage communication as a driver of intrauterine adhesion progression.COMMUNICATIONS BIOLOGY,8,(1)
MLA:
Dong, E.,et al."Single-cell sequencing uncovers disrupted stromal-macrophage communication as a driver of intrauterine adhesion progression".COMMUNICATIONS BIOLOGY 8..1(2025)