英国威康桑格研究所Roser Vento-Tormo和Krina T. Zondervan研究小组提出了人类子宫内膜单细胞参考图谱。相关论文发表在2024年8月28日出版的《自然—遗传学》杂志上。

课题组介绍了人类子宫内膜细胞图谱(HECA)，这是一个高分辨率的单细胞参考图谱(313,527个细胞)，结合了已发表的和新的63名患有和没有子宫内膜异位症的女性的子宫内膜单细胞转录组学数据集。

HECA分配共识并识别以前未报道的细胞类型，匹配到原位空间转录组，并用新的独立单核数据集(312,246个细胞核，63个供体)的进行验证。在功能方面，该课题组人员通过转化生长因子β (TGFβ)信号识别出复杂的基质-上皮细胞协调。

在基底细胞中，该课题组定义了成纤维细胞和表达祖细胞标记的上皮细胞群体之间的信号。HECA与大规模子宫内膜异位症全基因组关联研究数据的整合指出，去个体化的基质细胞和巨噬细胞最有可能在子宫内膜异位症中失调。HECA是研究子宫内膜生理和疾病、指导体外微生理系统发育的重要指标。

据了解，人类子宫内膜的复杂和动态的细胞组成仍然知之甚少。以前的子宫内膜单细胞图谱分析了很少的供体，并且在定义细胞类型方面缺乏共识。

附：英文原文

Title: An integrated single-cell reference atlas of the human endometrium

Author: Marekov, Magda, Garcia-Alonso, Luz, Moullet, Marie, Lorenzi, Valentina, Petryszak, Robert, Sancho-Serra, Carmen, Oszlanczi, Agnes, Icoresi Mazzeo, Cecilia, Wong, Frederick C. K., Kelava, Iva, Hoffman, Sophie, Krassowski, Micha, Garbutt, Kurtis, Gaitskell, Kezia, Yancheva, Slaveya, Woon, Ee Von, Male, Victoria, Granne, Ingrid, Hellner, Karin, Mahbubani, Krishnaa T., Saeb-Parsy, Kourosh, Lotfollahi, Mohammad, Prigmore, Elena, Southcombe, Jennifer, Dragovic, Rebecca A., Becker, Christian M., Zondervan, Krina T., Vento-Tormo, Roser

Issue&Volume: 2024-08-28

Abstract: The complex and dynamic cellular composition of the human endometrium remains poorly understood. Previous endometrial single-cell atlases profiled few donors and lacked consensus in defining cell types. We introduce the Human Endometrial Cell Atlas (HECA), a high-resolution single-cell reference atlas (313,527 cells) combining published and new endometrial single-cell transcriptomics datasets of 63 women with and without endometriosis. HECA assigns consensus and identifies previously unreported cell types, mapped in situ using spatial transcriptomics and validated using a new independent single-nuclei dataset (312,246 nuclei, 63 donors). In the functionalis, we identify intricate stromal–epithelial cell coordination via transforming growth factor beta (TGFβ) signaling. In the basalis, we define signaling between fibroblasts and an epithelial population expressing progenitor markers. Integration of HECA with large-scale endometriosis genome-wide association study data pinpoints decidualized stromal cells and macrophages as most likely dysregulated in endometriosis. The HECA is a valuable resource for studying endometrial physiology and disorders, and for guiding microphysiological in vitro systems development.

DOI: 10.1038/s41588-024-01873-w

Source: https://www.nature.com/articles/s41588-024-01873-w