Abstract Pelvic organ prolapse (POP) markedly affects the quality of life of women, including significant financial burden. Using single-cell RNA sequencing, we constructed a transcriptional profile of 30,452 single cells of the uterosacral ligament in POP and control samples, which has never been constructed before. We identified 10 major cell types, including smooth muscle cells, endothelial cells, fibroblasts, neutrophils, macrophages, monocytes, mast cells, T cells, B cells, and dendritic cells. We performed subpopulation analysis and pseudo-time analysis of POP primary cells, and explored differentially expressed genes. We verified previous cell clusters of human neutrophils of uterosacral ligaments. We found a significant reduction in receptor-ligand pairs related to ECM and cell adhesion between fibroblasts and endothelial cells in POP. The transcription factors related to the extracellular matrix, development, and immunity were identified in USL. Here we provide insight into the molecular mechanisms of POP and valuable information for future research directions.
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