首页|Comprehensive transcriptional atlas of human adenomyosis deciphered by the integration of single-cell RNA-sequencing and spatial transcriptomics

Comprehensive transcriptional atlas of human adenomyosis deciphered by the integration of single-cell RNA-sequencing and spatial transcriptomics

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Adenomyosis is a poorly understood gynecological disorder lacking effective treatments.Controversy persists regarding"invagination"and"metaplasia"theories.The endometrial-myometrial junction(EMJ)connects the endo-metrium 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 inva-sive 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 sub-populations within adenomyosis lesions identified,dysfunctional signaling,and EMJ abnormalities critical to devel-oping precise diagnostic and therapeutic strategies.

adenomyosissingle-cell RNA sequencingspatial transcriptomicsendometrial-myometrial junctionprogenitor cells

Tao Chen、Yiliang Xu、Xiaocui Xu、Jianzhang Wang、Zhiruo Qiu、Yayuan Yu、Xiaohong Jiang、Wanqi Shao、Dandan Bai、Mingzhu Wang、Shuyan Mei、Tao Cheng、Li Wu、Shaorong Gao、Xuan Che

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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

Key Laboratory of Animal Bioengineering and Disease Prevention of Shandong Province,College of Animal Science and Technology,Shandong Agricultural University,Taian 271018,China

Women's Hospital,School of Medicine,Zhejiang University,Hangzhou 310013,China

Postgraduate training base Alliance of Wenzhou Medical University,Wenzhou Medical University,Wenzhou 325035,China

Jiaxing University Master Degree Cultivation Base,Zhejiang Chinese Medical University,Hangzhou 310053,China

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

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaShanghai Key Laboratory of Maternal Fetal MedicineNatural Science Foundation of Zhejiang ProvinceJiaxing Municipal Public Welfare Research Project

322708403172100332270908mfmkf202201LTGY24H0400022021AY30004

2024

蛋白质与细胞

蛋白质与细胞

CSTPCD
影响因子:0.645
ISSN:
年,卷(期):2024.15(7)