Comprehensive transcriptional atlas of human adenomyosis deciphered by the integration of single-cell RNA-sequencing and spatial transcriptomics
Received date: 15 Dec 2023
Accepted date: 29 Feb 2024
Copyright
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.
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 . Comprehensive transcriptional atlas of human adenomyosis deciphered by the integration of single-cell RNA-sequencing and spatial transcriptomics[J]. Protein & Cell, 2024 , 15(7) : 530 -546 . DOI: 10.1093/procel/pwae012
1 |
Altmäe S, Koel M, Võsa U
|
2 |
Athanasiadis EI, Botthof JG, Andres H
|
3 |
Barker N, van Es JH, Kuipers J
|
4 |
Benagiano G, Brosens I. History of adenomyosis. Best Pract Res Clin Obstet Gynaecol2006; 20: 449-463.
|
5 |
Blache P, van de Wetering M, Duluc I
|
6 |
Bourdon M, Santulli P, Jeljeli M
|
7 |
Brabletz T, Jung A, Dag S
|
8 |
Chapron C, Vannuccini S, Santulli P
|
9 |
Chen Y, Zhu J, Chen L
|
10 |
Das A, Ash D, Fouda AY
|
11 |
Dason ES, Chan C, Sobel M. Diagnosis and treatment of adenomyosis. CMAJ2021; 193: E242.
|
12 |
Denzer L, Muranyi W, Schroten H
|
13 |
de Visser KE, Ciampricotti M, Michalak EM
|
14 |
Donnez J, Donnez O, Dolmans MM. Introduction: uterine adenomyosis, another enigmatic disease of our time. Fertil Steril2018; 109: 369-370.
|
15 |
García-Solares J, Donnez J, Donnez O
|
16 |
Guo SW. The pathogenesis of Adenomyosis vis-à-vis endometriosis. J Clin Med2020; 9: 485.
|
17 |
Harmsen MJ, Arduç A, Bleeker MCG
|
18 |
Huang H, Bhat A, Woodnutt G
|
19 |
Kho KA, Chen JS, Halvorson LM. Diagnosis, evaluation, and treatment of adenomyosis. JAMA2021; 326: 177-178.
|
20 |
Kobayashi H. Efficacy, adverse events, and challenges of dienogest in the management of symptomatic Adenomyosis: a comparison with different hormonal treatments. Gynecol Obstet Invest2023; 88: 71-80.
|
21 |
Kobayashi H, Kishi Y, Matsubara S. Mechanisms underlying adenomyosis-related fibrogenesis. Gynecol Obstet Invest2020; 85: 1-12.
|
22 |
Lai ZZ, Wang Y, Zhou WJ
|
23 |
La Porta S, Roth L, Singhal M
|
24 |
Lee HW, Xu Y, He L
|
25 |
Leung C, Tan SH, Barker N. Recent advances in Lgr5(+) stem cell research. Trends Cell Biol2018; 28: 380-391.
|
26 |
Liu Z, Sun Z, Liu H
|
27 |
Liu Z, Liu J, Chen T
|
28 |
Lv F, Li X, Wang Y et al. MAGP1 maintains tumorigenicity and angiogenesis of laryngeal cancer by activating Wnt/β-catenin/MMP7 pathway. Carcinogenesis 2023;bgad003.
|
29 |
Martire FG, Lazzeri L, Conway F
|
30 |
Moawad G, Youssef Y, Fruscalzo A
|
31 |
Naftalin J, Jurkovic D. The endometrial-myometrial junction:a fresh look at a busy crossing. Ultrasound Obstet Gynecol2009; 34: 1-11.
|
32 |
Pados G, Gordts S, Sorrentino F
|
33 |
Seishima R, Leung C, Yada S
|
34 |
Shi Y, Ping YF, Zhou W
|
35 |
Shih AJ, Adelson RP, Vashistha H
|
36 |
Signer RA, Magee JA, Salic A
|
37 |
Spears E, Neufeld KL. Novel double-negative feedback loop between adenomatous polyposis coli and Musashi1 in colon epithelia. J Biol Chem2011; 286: 4946-4950.
|
38 |
Stefater JA 3rd, Lewkowich I, Rao S
|
39 |
Stefater JA 3rd, Rao S, Bezold K
|
40 |
Stratopoulou CA, Donnez J, Dolmans MM. Origin and pathogenic mechanisms of uterine adenomyosis: what is known so far. Reprod Sci2021; 28: 2087-2097.
|
41 |
Tan Y, Flynn WF, Sivajothi S
|
42 |
Tempest N, Baker AM, Wright NA
|
43 |
Vannuccini S, Tosti C, Carmona F
|
44 |
Wan R, Yang G, Liu Q
|
45 |
Wang S, Li L, Cook C
|
46 |
Xu P, Ding S, Zhu L
|
47 |
Yildiz S, Kinali M, Wei JJ
|
48 |
Yu O, Schulze-Rath R, Grafton J
|
49 |
Zhang X, Qi C, Lin J. Enhanced expressions of matrix metalloproteinase (MMP)-2 and -9 and vascular endothelial growth factors (VEGF) and increased microvascular density in the endometrial hyperplasia of women with anovulatory dysfunctional uterine bleeding. Fertil Steril2010; 93: 2362-2367.
|
50 |
Zhang JB, Song W, Wang YY
|
51 |
Zhang J, Cai H, Sun L
|
52 |
Zhang M, Bazot M, Tsatoumas M
|
53 |
Zhu S, Ye L, Bennett S
|
/
〈 | 〉 |