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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Bibliographic Details
Published in:Protein & cell Vol. 15; no. 7; pp. 530 - 546
Main Authors: 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
Format: Journal Article
Language:English
Published: Germany Higher Education Press 01.07.2024
Springer Nature B.V
Oxford University Press
Subjects:
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
Online Access:Get full text
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Description
Summary: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.
Bibliography:single-cell RNA sequencing
Document received on :2023-12-15
endometrial-myometrial junction
spatial transcriptomics
adenomyosis
progenitor cells
Document accepted on :2024-02-29
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Tao Chen, Yiliang Xu, Xiaocui Xu and Jianzhang Wang contributed equally.
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ISSN:1674-800X
1674-8018
1674-8018
DOI:10.1093/procel/pwae012