An integrated single-cell reference atlas of the human endometrium.
Magda MarečkováLuz Garcia-AlonsoMarie MoulletValentina LorenziRobert PetryszakCarmen Sancho-SerraAgnes OszlancziCecilia Icoresi MazzeoFrederick C K WongIva KelavaSophie HoffmanMichal KrassowskiKurtis GarbuttKezia GaitskellSlaveya YanchevaEe Von WoonVictoria MaleIngrid GranneKarin HellnerKrishnaa T A MahbubaniKourosh Saeb ParsyMohammad LotfollahiElena PrigmoreJennifer SouthcombeRebecca A DragovicChristian M BeckerKrina T ZondervanRoser Vento-TormoPublished in: Nature genetics (2024)
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.
Keyphrases
- single cell
- rna seq
- transforming growth factor
- endothelial cells
- high throughput
- high resolution
- endometrial cancer
- genome wide association study
- epithelial mesenchymal transition
- stem cells
- randomized controlled trial
- clinical practice
- oxidative stress
- bone marrow
- cell cycle arrest
- mass spectrometry
- systematic review
- dna methylation
- electronic health record
- artificial intelligence
- signaling pathway
- deep learning
- kidney transplantation
- endoplasmic reticulum stress
- cell proliferation