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Single-cell analysis of uterosacral ligament revealed cellular heterogeneity in women with pelvic organ prolapse

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 for the first time, and 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE250414 | GEO | 2024/02/14

REPOSITORIES: GEO

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Gene expression profile in pelvic organ prolapse

Project description:Introduction and Hypothesis: Identify processes contributing to pelvic organ prolapse (POP) by transcriptional profiling of pelvic connective tissue in conjunction with light microscopy. Methods: We performed a frequency matched case-control study of women undergoing hysterectomy. Total RNA, extracted from uterosacral and round ligament samples used to generate labeled cRNA, was hybridized to microarrays and analyzed for the expression of 32,878 genes. Significance Analysis of Microarrays, (Stanford University, CA), identified differentially expressed genes used for ontoanalysis, and quantitative PCR (qPCR) confirmed results. Light microscopy confirmed tissue type and assessed inflammatory infiltration. Results: The analysis of thirty-four arrays revealed 249 differentially expressed genes with fold changes larger than 1.5 fold and false discovery rates M-bM-^IM-$5.2%. Immunity and Defense was the most significant biological process differentially expressed in POP. Selected qPCR confirmed 4 genes. Light microscopy showed no inflammatory infiltrates. Conclusions: Genes enriched for Immunity and Defense contribute to POP independent of inflammatory infiltrates. Keywords: whole tissue (endopelvic fascia) type comparison This was a group matched case control study of 8 women with pelvic organ prolapse versus 9 non-prolapse controls, both undergoing hysterectomy for benign conditions. Two separate pelvic support tissues were collected from each patient. The uterosacral ligament and round ligament tissue was removed at the time of hysterectomy, RNA was extracted and ABI whole genome chips used to identify differences in expression profiles of individual samples. Various ethnic groups, age groups and menopausal status were included.

2008-09-19 | E-GEOD-12852 | biostudies-arrayexpress

Profiles of Pelvic organ prolapse [miRNA-seq]

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Human POP analysis - Proteomics of Uterosacral Ligament Connective Tissue from Women With and Without Pelvic Organ Prolapse

Project description:Purpose: Damage to the uterosacral ligaments is an important contributor to uterine and vaginal prolapse. The aim of this study was to identify differentially expressed proteins in the uterosacral ligaments of women with and without pelvic organ prolapse and analyze their relationships to cellular mechanisms involved in the pathogenesis of pelvic organ prolapse. Experimental Design: Uterosacral ligament connective tissue from four patients with pelvic organ prolapse and four control women underwent iTRAQ analysis followed by Ingenuity Pathway Analysis of differentially expressed proteins. Differentially expressed proteins were valideated using western blot analysis. Results: A total of 1789 unique protein sequences were identified in the uterosacral ligament connective tissues. 88 proteins had expression levels that were significantly different between prolapse and control groups (≥1.2-fold). Ingenuity pathway analysis demonstrated 14 differentially expressed proteins that were associated with "Connective Tissue Function". Among them, fibromodulin(FMOD), Collagen alpha-1 (XIV) chain(COL14A1), Calponin-1 (CNN-1), Tenascin (TNC), and Galectin-1(LGALS1 appeared most likely to play a role in the etiology of pelvic organ prolapse. Conclusions and clinical relevence: We identified at least 6 proteins not previously associated with the pathogenesis of pelvic organ prolapse with biologic functions that suggest a plausible relationship to the disorder. These results may be helpful for furthering our understanding of the pathophysiological mechanisms of pelvic organ prolapse.

2018-12-10 | PXD011467 | Pride

Profiles of Pelvic organ prolapse [mRNA-seq, lncRNA-seq, circRNA-seq]

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Micro-array analysis of the anterior vaginal wall from premenopausal patients with Pelvic Organ Prolapse (POP)

Project description:Pelvic organ prolapse (POP) is a common multifactorial disease in a heterogeneous population of women. Due to this heterogeneity, the underlying molecular mechanisms contributing to the pathogenesis of POP are still unclear. We sought to identify dysregulated pathways by comparing gene expression profiles of prolapsed and non- prolapsed anterior vaginal wall tissue within the same patient. Biopsies were collected from 12 premenopausal women undergoing prolapse surgery (cystocele POP-Q stage ≥ 2). A full thickness anterior vaginal wall sample was taken from the POP site during anterior colporrhaphy. An additional sample was taken from the non-prolapsed apex of the anterior vaginal cuff. Micro-array analysis was performed using whole genome GE 4x44K microarrays. Beside a significance analysis of micro-array (SAM), also a visual cluster analysis was performed. 12 women with POP: 12 biopsies anterior vaginal wall (POP site) versus 12 biopies precervical anterior vaginal wall ( non POP site)

2015-07-31 | E-GEOD-53868 | biostudies-arrayexpress

Micro-array analysis of the anterior vaginal wall from premenopausal patients with Pelvic Organ Prolapse (POP)

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Differential gene expression in uterosacral ligament from patients with recurrent and primary pelvic organ prolapse

Project description:Objective: The objective of this study was to profile differential gene expression in three distinct patient groups. Study Design: The groups consisted of women with recurrent POP, women with primary POP and women without POP. Whole human genome DNA microarrays were used to evaluate differential gene expression in uterosacral ligament (USL) tissues. Results: 10 genes of interest were identified in USL. Eight genes were over expressed 30-fold or greater, and two genes were under expressed. Confirmation of differential gene expression used the technique of real-time RT-PCR. Five of the substantially over expressed genes functioned in the distribution, metabolism or deposition of adipose tissue. Homeobox genes D10 and D11 were under expressed. Conclusions: The differential gene expression seen in the USL tissues in women with recurrent POP suggests that USLs are weakened by changes directed by these genes.

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