Author:
Marečková Magda,Garcia-Alonso Luz,Moullet Marie,Lorenzi Valentina,Petryszak Robert,Sancho-Serra Carmen,Oszlanczi Agnes,Mazzeo Cecilia Icoresi,Hoffman Sophie,Krassowski Michał,Garbutt Kurtis,Kelava Iva,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
Abstract
AbstractThe human endometrium, the inner lining of the uterus, exhibits complex, dynamic changes throughout the menstrual cycle in response to ovarian hormones. Aberrant response of endometrial cells to hormones is associated with multiple disorders, including endometriosis. Previous single-cell studies of the endometrium profiled a limited number of donors and lacked consensus in defining cell types and states. Here, we introduce the Human Endometrial Cell Atlas (HECA), a high-resolution single-cell reference atlas, combining published and newly generated single-cell transcriptomics datasets of endometrial biopsies of women with and without endometriosis. The HECA assigned consensus cell types and states, and uncovered novel ones, which we mapped in situ using spatial transcriptomics. We quantified how coordinated interactions between cell states in space and time contribute to endometrial regeneration and differentiation. In the continuously changingfunctionalislayer, we identified an intricate coordination of TGFβ signalling between stromal and epithelial cells, likely crucial for cell differentiation. In thebasalislayer, we defined signalling between fibroblasts and a new epithelial cell population expressing epithelial stem/progenitor markers, suggesting their role in endometrial regeneration. Additionally, integrating the HECA single-cell data with genome-wide association study data and comparing endometrial samples from women with and without endometriosis, we pinpointed subsets of decidualised stromal cells and macrophages as the most dysregulated cell states in endometriosis. Overall, the HECA is an invaluable resource for studying endometrial physiology, investigating endometrial disorders, and guiding the creation of endometrial microphysiologicalin vitrosystems.
Publisher
Cold Spring Harbor Laboratory