Mapping Single-Cell Transcriptomes of Endometrium Reveals Potential Biomarkers in Endometrial Cancer.

Area of Science:

• Reproductive biology
• Genomics
• Immunology

Background:

• Endometrial cell heterogeneity and dynamics are crucial for menstrual cycle function.
• Endometrial dysfunction is linked to gynecological diseases.
• Understanding the immune microenvironment's transcriptional programs is key to endometrial biology.

Purpose of the Study:

• To comprehensively analyze the single-cell transcriptome of human endometrium across the menstrual cycle.
• To identify cell types, transcription factor activities, and cell-cell interactions.
• To reveal molecular subtypes of endometrial carcinoma (EC) and their pathogenesis.

Main Methods:

• Single-cell RNA sequencing of 59,397 cells from ten human endometrium samples.
• Identification of endometrial cell subtypes (perivascular, epithelial, fibroblast).
• Inference of cell type-specific transcription factor activities and integration with EC bulk transcriptomes.

Main Results:

• Characterization of two perivascular, four epithelial, and four fibroblast cell subtypes.
• Identification of critical transcription factors regulating endometrial cell function.
• Discovery of five RNA-based molecular subtypes of endometrial carcinoma with distinct clinical features.

Conclusions:

• The study elucidates the dynamic immune microenvironment of the endometrium.
• Novel insights are provided for RNA-based therapeutic strategies for endometriosis and endometrial carcinoma.
• Highlights the importance of transcriptional regulation in endometrial health and disease.