From Invaginating Site to Deep Lesion: Spatial Transcriptomics Unravels Ectopic Endometrial Penetration Features in Adenomyosis
Abstract Adenomyosis, characterized by clinical intractability, significantly impacts female fertility and life quality due to the absence of definitive diagnostic markers and effective treatment options. The invagination theory is a primary hypothesis for adenomyosis, but the underlying molecular m...
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| Format: | Article |
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202411752 |
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| author | Boyu Li Jia Qi Yumeng Cao Yijing Long Zhe Wei Wang‐Sheng Wang Shuanggang Hu Yuan Wang Qinling Zhu Xiao Hu Zhe Sun Jie Zhu Taiyang Ye Yejie Yao Yiwen Meng Xuejiao Bian Xinyi Dong Hengyu Guan Yunfei Huang Yun Sun |
| author_facet | Boyu Li Jia Qi Yumeng Cao Yijing Long Zhe Wei Wang‐Sheng Wang Shuanggang Hu Yuan Wang Qinling Zhu Xiao Hu Zhe Sun Jie Zhu Taiyang Ye Yejie Yao Yiwen Meng Xuejiao Bian Xinyi Dong Hengyu Guan Yunfei Huang Yun Sun |
| author_sort | Boyu Li |
| collection | DOAJ |
| description | Abstract Adenomyosis, characterized by clinical intractability, significantly impacts female fertility and life quality due to the absence of definitive diagnostic markers and effective treatment options. The invagination theory is a primary hypothesis for adenomyosis, but the underlying molecular mechanisms remain unclear. In this study, a spatial transcriptional landscape of adenomyosis with an evident invagination structure is mapped from the endometrial invaginating site to ectopic lesions utilizing spatial transcriptomics and single‐cell RNA sequencing. In addition, the authors employ bulk RNA sequencing deconvolution to assess the significance of core spatial ecotypes, use histological techniques to target specific cell types, and conduct in vitro experiments for validation. At the invagination site, SFRP5+ epithelial cells promote endometrial proliferation and angiogenesis through secretion of IHH. During the invading process, ESR1+ smooth muscle cells (SMCs) facilitate invasion by creating migratory tracts via collagen degradation. Within deep lesions, CNN1+ stromal fibroblasts induce fibrosis by undergoing a fibroblast‐to‐myofibroblast transition (FMT) in response to pathologic profibrogenic signals in the microenvironment of lesions. This work offers an in‐depth understanding of the molecular mechanisms underlying the pathological processes of adenomyosis with invagination. Furthermore, this work introduces the first transcriptomics web source of adenomyosis, which is expected to be a valuable resource for subsequent research. |
| format | Article |
| id | doaj-art-bfa44c3c856a4e2bb6f01b80279e0f22 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-bfa44c3c856a4e2bb6f01b80279e0f222025-08-20T02:34:43ZengWileyAdvanced Science2198-38442025-05-011220n/an/a10.1002/advs.202411752From Invaginating Site to Deep Lesion: Spatial Transcriptomics Unravels Ectopic Endometrial Penetration Features in AdenomyosisBoyu Li0Jia Qi1Yumeng Cao2Yijing Long3Zhe Wei4Wang‐Sheng Wang5Shuanggang Hu6Yuan Wang7Qinling Zhu8Xiao Hu9Zhe Sun10Jie Zhu11Taiyang Ye12Yejie Yao13Yiwen Meng14Xuejiao Bian15Xinyi Dong16Hengyu Guan17Yunfei Huang18Yun Sun19Department of Reproductive Medicine Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. ChinaDepartment of Reproductive Medicine Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. ChinaDepartment of Reproductive Medicine Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. ChinaDepartment of Reproductive Medicine Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. ChinaDepartment of Reproductive Medicine Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. ChinaDepartment of Reproductive Medicine Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. ChinaDepartment of Reproductive Medicine Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. ChinaDepartment of Reproductive Medicine Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. ChinaDepartment of Reproductive Medicine Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. ChinaDepartment of Reproductive Medicine Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. ChinaDepartment of Reproductive Medicine Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. ChinaDepartment of Obstetrics and Gynecology Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200127 P. R. ChinaDepartment of Obstetrics and Gynecology Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200127 P. R. ChinaDepartment of Reproductive Medicine Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. ChinaDepartment of Reproductive Medicine Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. ChinaDepartment of Reproductive Medicine Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. ChinaDepartment of Reproductive Medicine Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. ChinaDepartment of Reproductive Medicine Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. ChinaDepartment of Reproductive Medicine Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. ChinaDepartment of Reproductive Medicine Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. ChinaAbstract Adenomyosis, characterized by clinical intractability, significantly impacts female fertility and life quality due to the absence of definitive diagnostic markers and effective treatment options. The invagination theory is a primary hypothesis for adenomyosis, but the underlying molecular mechanisms remain unclear. In this study, a spatial transcriptional landscape of adenomyosis with an evident invagination structure is mapped from the endometrial invaginating site to ectopic lesions utilizing spatial transcriptomics and single‐cell RNA sequencing. In addition, the authors employ bulk RNA sequencing deconvolution to assess the significance of core spatial ecotypes, use histological techniques to target specific cell types, and conduct in vitro experiments for validation. At the invagination site, SFRP5+ epithelial cells promote endometrial proliferation and angiogenesis through secretion of IHH. During the invading process, ESR1+ smooth muscle cells (SMCs) facilitate invasion by creating migratory tracts via collagen degradation. Within deep lesions, CNN1+ stromal fibroblasts induce fibrosis by undergoing a fibroblast‐to‐myofibroblast transition (FMT) in response to pathologic profibrogenic signals in the microenvironment of lesions. This work offers an in‐depth understanding of the molecular mechanisms underlying the pathological processes of adenomyosis with invagination. Furthermore, this work introduces the first transcriptomics web source of adenomyosis, which is expected to be a valuable resource for subsequent research.https://doi.org/10.1002/advs.202411752adenomyosisfibrosisinvaginationinvasionspatial transcriptomics |
| spellingShingle | Boyu Li Jia Qi Yumeng Cao Yijing Long Zhe Wei Wang‐Sheng Wang Shuanggang Hu Yuan Wang Qinling Zhu Xiao Hu Zhe Sun Jie Zhu Taiyang Ye Yejie Yao Yiwen Meng Xuejiao Bian Xinyi Dong Hengyu Guan Yunfei Huang Yun Sun From Invaginating Site to Deep Lesion: Spatial Transcriptomics Unravels Ectopic Endometrial Penetration Features in Adenomyosis Advanced Science adenomyosis fibrosis invagination invasion spatial transcriptomics |
| title | From Invaginating Site to Deep Lesion: Spatial Transcriptomics Unravels Ectopic Endometrial Penetration Features in Adenomyosis |
| title_full | From Invaginating Site to Deep Lesion: Spatial Transcriptomics Unravels Ectopic Endometrial Penetration Features in Adenomyosis |
| title_fullStr | From Invaginating Site to Deep Lesion: Spatial Transcriptomics Unravels Ectopic Endometrial Penetration Features in Adenomyosis |
| title_full_unstemmed | From Invaginating Site to Deep Lesion: Spatial Transcriptomics Unravels Ectopic Endometrial Penetration Features in Adenomyosis |
| title_short | From Invaginating Site to Deep Lesion: Spatial Transcriptomics Unravels Ectopic Endometrial Penetration Features in Adenomyosis |
| title_sort | from invaginating site to deep lesion spatial transcriptomics unravels ectopic endometrial penetration features in adenomyosis |
| topic | adenomyosis fibrosis invagination invasion spatial transcriptomics |
| url | https://doi.org/10.1002/advs.202411752 |
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