A new perspective on endometriosis: Integrating eQTL mendelian randomization with transcriptomics and single-cell...

Area of Science:

• Genetics and Molecular Biology
• Reproductive Medicine
• Immunology

Background:

• Endometriosis, characterized by endometrial cell migration outside the uterus, is increasingly prevalent.
• Limited research exists on endometriosis genetics and its molecular mechanisms.
• Understanding these mechanisms is crucial for identifying new therapeutic targets.

Purpose of the Study:

• To investigate the molecular mechanisms of endometriosis development.
• To identify novel genetic targets for endometriosis.
• To integrate multi-omics data including gene chips, single-cell mapping, and GWAS.

Main Methods:

• Downloaded gene expression data from the Gene Expression Omnibus (GEO) for normal, eutopic, and ectopic endometrial tissues.
• Performed differential gene expression (DEG), expression quantitative trait loci (eQTL), and Mendelian randomization (MR) analyses.
• Analyzed single-cell atlas datasets to explore disease mechanisms and cell communication.

Main Results:

• Identified 30 candidate biomarker genes by intersecting MR results with DEGs.
• Highlighted four key genes: HNMT, CCDC28A, FADS1, and MGRN1, showing differential expression.
• Found evidence of epithelial-mesenchymal transition (EMT) in eutopic endometrium and identified interactions between ciliated epithelial cells and immune cells (NK, T, B cells).

Conclusions:

• Identified four novel biomarker genes for endometriosis.
• Provided evidence for EMT in eutopic endometrium.
• Suggests endometriosis progression is linked to EMT and immune microenvironment alterations following ciliated epithelial cell damage.