September 2024 | Magda Marečková, Luz Garcia-Alonso, Marie Mouillet, Valentina Lorenzi, Robert Petryszak, Carmen Sancho-Serra, Agnes Oszlanzci, Cecilia Icoresi Mazzeo, Frederick C. K. Wong, Iva Kelava, Sophie Hoffman, Michal Krassowski, Kurtis Garbutt, Kezia Gaitskell, Slaveya Yancheva, Ee Von Woon, Victoria Male, Ingrid Granne, Karin Hellner, Krishna T. Mahbubani, Kourosh Saeb-Parsy, Mohammad Lotfolahi, Elena Prigmore, Jennifer Southcombe, Rebecca A. Dragovic, Christian M. Becker, Krina T. Zondervan & Roser Vento-Tormo
The article presents the Human Endometrial Cell Atlas (HECA), a comprehensive single-cell reference atlas of the human endometrium, integrating published and newly generated datasets from 63 women with and without endometriosis. The HECA includes 313,527 cells and 312,246 nuclei, providing a high-resolution view of endometrial cell types and states. It identifies previously unreported cell types, including an epithelial CDH2+ population in the basalis and distinct populations of functionalis epithelial and stromal cells. The atlas maps these cells in situ using spatial transcriptomics and validates them with a new single-nuclei dataset. The HECA reveals intricate stromal-epithelial coordination via TGFβ signaling and defines signaling between fibroblasts and an epithelial population expressing progenitor markers in the basalis. Integration with genome-wide association study data highlights decidualized stromal cells and macrophages as likely dysregulated in endometriosis. The HECA serves as a valuable resource for studying endometrial physiology and disorders, and for guiding in vitro systems development. The endometrium is complex, with two layers (functionalis and basalis) that undergo dynamic changes during the menstrual cycle. The functionalis layer is involved in embryo implantation, while the basalis layer regenerates after menstruation. The endometrium contains various cell types, including epithelial, stromal, fibroblast, perivascular, and endothelial cells, as well as immune cells. The HECA provides a detailed map of these cells, their interactions, and their roles in endometrial function and disease. The study highlights the importance of cell-cell communication in endometrial functioning and menstrual cycle progression. The HECA is a significant resource for understanding endometrial biology and for developing new therapies for endometrial disorders.The article presents the Human Endometrial Cell Atlas (HECA), a comprehensive single-cell reference atlas of the human endometrium, integrating published and newly generated datasets from 63 women with and without endometriosis. The HECA includes 313,527 cells and 312,246 nuclei, providing a high-resolution view of endometrial cell types and states. It identifies previously unreported cell types, including an epithelial CDH2+ population in the basalis and distinct populations of functionalis epithelial and stromal cells. The atlas maps these cells in situ using spatial transcriptomics and validates them with a new single-nuclei dataset. The HECA reveals intricate stromal-epithelial coordination via TGFβ signaling and defines signaling between fibroblasts and an epithelial population expressing progenitor markers in the basalis. Integration with genome-wide association study data highlights decidualized stromal cells and macrophages as likely dysregulated in endometriosis. The HECA serves as a valuable resource for studying endometrial physiology and disorders, and for guiding in vitro systems development. The endometrium is complex, with two layers (functionalis and basalis) that undergo dynamic changes during the menstrual cycle. The functionalis layer is involved in embryo implantation, while the basalis layer regenerates after menstruation. The endometrium contains various cell types, including epithelial, stromal, fibroblast, perivascular, and endothelial cells, as well as immune cells. The HECA provides a detailed map of these cells, their interactions, and their roles in endometrial function and disease. The study highlights the importance of cell-cell communication in endometrial functioning and menstrual cycle progression. The HECA is a significant resource for understanding endometrial biology and for developing new therapies for endometrial disorders.