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

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 c...

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Vydáno v:	Protein & cell Ročník 15; číslo 7; s. 530 - 546
Hlavní autoři:	Chen, Tao, Xu, Yiliang, Xu, Xiaocui, Wang, Jianzhang, Qiu, Zhiruo, Yu, Yayuan, Jiang, Xiaohong, Shao, Wanqi, Bai, Dandan, Wang, Mingzhu, Mei, Shuyan, Cheng, Tao, Wu, Li, Gao, Shaorong, Che, Xuan
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Germany Higher Education Press 01.07.2024 Springer Nature B.V Oxford University Press
Témata:	adenomyosis Adenomyosis - genetics Adenomyosis - metabolism Adenomyosis - pathology Angiogenesis Angiopoietin Cell interactions endometrial-myometrial junction Endometrium Endometrium - metabolism Endometrium - pathology Endothelial cells Female Humans Lesions Metaplasia Myometrium Myometrium - metabolism Myometrium - pathology Pleiotrophin Progenitor cells Sequence Analysis, RNA Single-Cell Analysis single-cell RNA sequencing spatial transcriptomics Transcriptome Transcriptomics Vascular endothelial growth factor Wnt protein single-cell RNA sequencing progenitor cells endometrial-myometrial junction spatial transcriptomics adenomyosis
ISSN:	1674-800X, 1674-8018, 1674-8018
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Shrnutí:	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.
Bibliografie:	single-cell RNA sequencing Document received on :2023-12-15 endometrial-myometrial junction spatial transcriptomics adenomyosis progenitor cells Document accepted on :2024-02-29 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Tao Chen, Yiliang Xu, Xiaocui Xu and Jianzhang Wang contributed equally. Lead contact.
ISSN:	1674-800X 1674-8018 1674-8018
DOI:	10.1093/procel/pwae012