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Recently, Chen Xiaojun of the Affiliated Obstetrics and Gynecology Hospital of Fudan University and Zhao Bing, State Key Laboratory of Genetic Engineering of Fudan University, published a paper in Nature Communications, which mapped the dynamic map of different cell subsets of cells during the transition from normal endometrial to endometrioid carcinoma through single-cell transcriptomic analysis, revealing the potential cell origin and pathological development process of endometrium-like carcinoma [1].
。
Dr.
Ren Xiaojun of the Obstetrics and Gynecology Hospital of Fudan University is the first author
of this paper.
Chen Xiaojun and Zhao Bing are co-corresponding authors of this article
Research background
Endometrial cancer is one of the most common gynecologic malignancies, and its incidence is on the rise worldwide
.
Endometrioid carcinoma is the most common type of endometrial cancer, and in-depth analysis of its pathogenesis is conducive to the development of accurate and effective new prevention and treatment strategies
.
The endometrium contains multiple types of cells such as epithelial, interstitial, and immunological, and multi-lineage cell differentiation and fate remodeling occur during the menstrual cycle, thereby maintaining endometrial physiological function and homeostasis
.
Although previous studies have depicted normal endometrial cell composition [2], the dynamics of cell subsets during the evolution of normal endometrium to endometrioid carcinoma are unclear
.
Research content
The study revealed the characteristic changes
of increased endometrial epithelial cells and decreased mesenchymal cells during the development of endometrioid carcinoma by single-cell transcriptomic sequencing analysis of normal endometrium, atypical hyperplasia endometrium, and endometrium-like carcinoma.
Bioinformatics analysis further suggests that endometrioid carcinoma may have originated in epithelial cells rather than mesenchymal cells
.
Further subdivision of epithelial cell subsets found that nonciliary gland epithelial cells are a potential source of endometrioid carcinoma, and the available evidence does not support an evolutionary relationship
between the stroma and epithelium.
The study also found that LCN2+/SAA1/2+ epithelial cells are characteristic subsets during the development of endometrioid carcinoma, which appear in atypical hyperplasia foci and persist in endometrioid carcinoma, which is of great significance
for the diagnosis of endometrial cancer.
In addition, the study also depicts important features
of the tumor microenvironment during the development of endometrial carcinoma.
Among them, although the number of interstitial cell subsets did not change significantly, the endometrial epithelial organoid interstitial co-culture experiment showed that compared with normal mesenchymal cells, the ability of cancer mesenchymal cells to stimulate the expression of stem genes in the epithelium was significantly enhanced.
Significant changes in the subset of immune cells during the occurrence of endometrial carcinoma are manifested as a decrease in the proportion of cytotoxic T cells and an increase in the proportion of regulatory T cells, suggesting that immune evasion may play an important role
in the development of endometrial carcinoma.
In summary, this study revealed the dynamic evolution of cell subsets during the evolution of normal endometrium to endometrioid carcinoma through single-cell transcriptomic sequencing, which provided new clues
for the origin, early diagnosis and clinical treatment of endometrial cancer cells.
References
1.
Ren, X.
et al.
Single-cell transcriptomic analysis highlights origin and pathological process of human endometrioid endometrial carcinoma.
Nat Commun 13, 6300 (2022).
2.
Wang, W.
et al.
Single-cell transcriptomic atlas of the human endometrium during the menstrual cycle.
Nat Med 26, 1644-1653 (2020).
Author: Ren Xiaojun
Editor/Typesetting: Wang Lu
Review: Qiu Jia
【Note】This article is a doctor's newspaper with the consent of the author to reprint the article, any institution or individual need to reprint, please contact the original author for authorization!
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