An integrated single-cell reference atlas of the human endometrium.

Area of Science:

• Reproductive Biology
• Genomics
• Cell Biology

Background:

• The human endometrium's cellular complexity and dynamics are not fully understood.
• Previous single-cell atlases of the endometrium had limited donor numbers and lacked consensus on cell type definitions.

Purpose of the Study:

• To create a high-resolution, comprehensive single-cell reference atlas of the human endometrium.
• To identify novel cell types and intercellular signaling pathways.
• To investigate cellular dysregulation in endometriosis.

Main Methods:

• Combined published and new single-cell transcriptomics data from 63 women.
• Utilized spatial transcriptomics for in situ mapping of cell types.
• Validated findings with an independent single-nuclei dataset.
• Integrated atlas data with endometriosis genome-wide association study (GWAS) data.

Main Results:

• Established the Human Endometrial Cell Atlas (HECA) with 313,527 cells.
• Identified consensus cell types and previously unreported populations.
• Revealed intricate stromal-epithelial cell coordination via transforming growth factor beta (TGFβ) signaling in the functionalis.
• Defined signaling between fibroblasts and progenitor-like epithelial cells in the basalis.
• Pinpointed decidualized stromal cells and macrophages as potentially dysregulated in endometriosis.

Conclusions:

• HECA provides a valuable resource for endometrial research.
• The atlas enhances understanding of endometrial physiology and pathophysiology.
• Findings guide the development of in vitro microphysiological systems for studying the endometrium.