TY - JOUR KW - RNA sequencing KW - Transcriptomics AU - Magda Marečková AU - Luz Garcia-Alonso AU - Marie Moullet AU - Valentina Lorenzi AU - Robert Petryszak AU - Carmen Sancho-Serra AU - Agnes Oszlanczi AU - Cecilia Icoresi Mazzeo AU - Frederick C. K. Wong AU - Iva Kelava AU - Sophie Hoffman AU - Michał Krassowski AU - Kurtis Garbutt AU - Kezia Gaitskell AU - Slaveya Yancheva AU - Ee Von Woon AU - Victoria Male AU - Ingrid Granne AU - Karin Hellner AU - Krishnaa T. Mahbubani AU - Kourosh Saeb-Parsy AU - Mohammad Lotfollahi AU - Elena Prigmore AU - Jennifer Southcombe AU - Rebecca A. Dragovic AU - Christian M. Becker AU - Krina T. Zondervan AU - Roser Vento-Tormo AB - 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. BT - Nature Genetics DA - 2024-09 DO - 10.1038/s41588-024-01873-w IS - 9 LA - en N2 - 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. PY - 2024 SP - 1925 EP - 1937 T2 - Nature Genetics TI - An integrated single-cell reference atlas of the human endometrium UR - https://www.nature.com/articles/s41588-024-01873-w VL - 56 Y2 - 2024-11-26 SN - 1546-1718 ER -