An integrated single-cell reference atlas of the human endometrium

Magda Marečková, Luz García‐Alonso, Luz Garcia-Alonso, Marie Moullet, Valentina Lorenzi, Robert Petryszak, Carmen Sancho‐Serra, Carmen Sancho-Serra, Ágnes Oszlánczi, Cecilia Mazzeo, Cecilia Icoresi Mazzeo, Frederick C.K. Wong, Iva Kelava, Sophie Hoffman, Michał Krassowski, Kurtis Garbutt, 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, Jennifer Southcombe, Rebecca Dragovic, Rebecca A Dragovic, Christian M. Becker, Krina T. Zondervan, Roser Vento‐Tormo
Nature genetics · 2024 · vol. 56(9) , pp. 1925–1937 · doi:10.1038/s41588-024-01873-w · PMID:39198675 · PMC11387200 · W4401978437
article OA: gold CC0 ⤵ 24 in-corpus citations
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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.

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Outcome instruments

rASRM

Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometrium Endometrium Endometrium Endometrium

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