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Single-cell transcriptomic analysis highlights origin and pathological process of human endometrioid endometrial carcinoma

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  • Xiaojun Ren

    (Obstetrics and Gynecology Hospital of Fudan University
    Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases)

  • Jianqing Liang

    (Fudan University
    Fudan University)

  • Yiming Zhang

    (Fudan University
    Fudan University)

  • Ning Jiang

    (Fudan University
    Fudan University)

  • Yuhui Xu

    (Obstetrics and Gynecology Hospital of Fudan University
    Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases)

  • Mengdi Qiu

    (Fudan University
    Fudan University)

  • Yiqin Wang

    (Obstetrics and Gynecology Hospital of Fudan University
    Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases)

  • Bing Zhao

    (Fudan University
    Fudan University)

  • Xiaojun Chen

    (Obstetrics and Gynecology Hospital of Fudan University
    Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases)

Abstract

Endometrial cancers are complex ecosystems composed of cells with distinct phenotypes, genotypes, and epigenetic states. Current models do not adequately reflect oncogenic origin and pathological progression in patients. Here we use single-cell RNA sequencing to profile cells from normal endometrium, atypical endometrial hyperplasia, and endometrioid endometrial cancer (EEC), which altogether represent the step-by-step development of endometrial cancer. We find that EEC originates from endometrial epithelial cells but not stromal cells, and unciliated glandular epithelium is the source of EEC. We also identify LCN2 + /SAA1/2 + cells as a featured subpopulation of endometrial tumorigenesis. Finally, the stromal niche and immune environment changes during EEC progression are described. This study elucidates the evolution of cell populations in EEC development at single-cell resolution, which would provide a direction to facilitate EEC research and diagnosis.

Suggested Citation

  • Xiaojun Ren & Jianqing Liang & Yiming Zhang & Ning Jiang & Yuhui Xu & Mengdi Qiu & Yiqin Wang & Bing Zhao & Xiaojun Chen, 2022. "Single-cell transcriptomic analysis highlights origin and pathological process of human endometrioid endometrial carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33982-7
    DOI: 10.1038/s41467-022-33982-7
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    References listed on IDEAS

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    1. Zhaohui Chen & Lijie Zhou & Lilong Liu & Yaxin Hou & Ming Xiong & Yu Yang & Junyi Hu & Ke Chen, 2020. "Single-cell RNA sequencing highlights the role of inflammatory cancer-associated fibroblasts in bladder urothelial carcinoma," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    2. Gioele La Manno & Ruslan Soldatov & Amit Zeisel & Emelie Braun & Hannah Hochgerner & Viktor Petukhov & Katja Lidschreiber & Maria E. Kastriti & Peter Lönnerberg & Alessandro Furlan & Jean Fan & Lars E, 2018. "RNA velocity of single cells," Nature, Nature, vol. 560(7719), pages 494-498, August.
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