An integrated single-cell reference atlas of the human endometrium
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Published version
Author(s)
Type
Journal Article
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.
Date Issued
2024-09
Date Acceptance
2024-07-17
Citation
Nature Genetics, 2024, 56 (9), pp.1925-1937
ISSN
1061-4036
Publisher
Nature Research
Start Page
1925
End Page
1937
Journal / Book Title
Nature Genetics
Volume
56
Issue
9
Copyright Statement
© The Author(s) 2024 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.nature.com/articles/s41588-024-01873-w
Subjects
ANGIOGENESIS
EPITHELIUM
EXPRESSION
Genetics & Heredity
GROWTH-FACTORS
IN-VITRO
Life Sciences & Biomedicine
LONG-TERM
MACROPHAGE
MENSTRUAL-CYCLE
PHYSIOLOGY
Science & Technology
TROPHOBLAST
Publication Status
Published
Date Publish Online
2024-08-28