机构地区:[1]Department of Obstetrics and Gynecology,Affiliated Women and Children Hospital of Jiaxing University,Jiaxing 314000,China [2]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 [3]Key Laboratory of Animal Bioengineering and Disease Prevention of Shandong Province,College of Animal Science and Technology,Shandong Agricultural University,Taian 271018,China [4]Women’s Hospital,School of Medicine,Zhejiang University,Hangzhou 310013,China [5]Postgraduate training base Alliance of Wenzhou Medical University,Wenzhou Medical University,Wenzhou 325035,China [6]Jiaxing University Master Degree Cultivation Base,Zhejiang Chinese Medical University,Hangzhou 310053,China [7]Shanghai Key Laboratory of Maternal Fetal Medicine,Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology,Clinical and Translational Research Center,Shanghai First Maternity and Infant Hospital,School of Life Sciences and Technology,Tongji University,Shanghai 200092,China
出 处:《Protein & Cell》2024年第7期530-546,共17页蛋白质与细胞(英文版)
基 金:National Natural Science Foundation of China(Nos.32270840,31721003 and 32270908);Shanghai Key Laboratory of Maternal Fetal Medicine(No.mfmkf202201);Natural Science Foundation of Zhejiang Province(No.LTGY24H040002);Jiaxing Municipal Public Welfare Research Project(No.2021AY30004).
摘 要: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.
关 键 词:ADENOMYOSIS single-cell RNA sequencing spatial transcriptomics endometrial-myometrial junction progenitor cells
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