An integrated single-cell reference atlas of the human endometrium

Magda Marečková, Luz Garcia-Alonso, Luz García‐Alonso, Marie Moullet, Valentina Lorenzi, Robert Petryszak, Carmen Sancho‐Serra, Ágnes Oszlánczi, Cecilia Mazzeo, Sophie Hoffman, Michał Krassowski, Kurtis Garbutt, Iva Kelava, Kezia Gaitskell, Slaveya Yancheva, Ee Von Woon, Victoria Male, Ingrid Granne, Karin Hellner, Krishnaa T. Mahbubani, Kourosh Saeb‐Parsy, Mohammad Lotfollahi, Elena Prigmore, Jennifer H. Southcombe, Rebecca Dragovic, Christian M. Becker, Krina T. Zondervan, Roser Vento‐Tormo
In: bioRxiv · 2023 · doi:10.1101/2023.11.03.564728 · W4388374250
preprint OA: green CC0 ⤵ 1 in-corpus citation
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This study established the Human Endometrial Cell Atlas (HECA), a comprehensive single-cell reference integrating multiple datasets to map endometrial cell types, states, and their spatiotemporal interactions, identifying dysregulated cell states in endometriosis.

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Abstract

Abstract The 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 changing functionalis layer, we identified an intricate coordination of TGFβ signalling between stromal and epithelial cells, likely crucial for cell differentiation. In the basalis layer, 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 microphysiological in vitro systems.

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endometriosis

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