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Cell type specific differences in the transcriptomes of adipose derived stem cells and vaginal fibroblasts in patients with pelvic organ prolapse

ABSTRACT: The purpose of the study was to understand the molecular phenotypes of adipose-derived stem cells (ASCs) and vaginal fibroblasts (VFBs) and whether pelvic organ prolapse (POP) affects their biological properties. We performed RNA sequencing of paired ASCs and VFBs from six patients with POP and six controls (CTRL). We found no differentially expressed genes (DEG) between POP and CTRL in ASCs and VFBs. Less stringent statistical analysis of VFBs transcriptome showed 23 genes with higher and 29 genes with 2-fold lower expression in POP compared to CTRL. Among the latter were five genes involved in the synaptogenesis pathway found to be significant. We were only able to validate POP related differences for VLDLR protein. We found 508 DEG with 4-fold difference between ASCs and VFBs (when POP and CTRL samples were combined for each cell type). The DEG with higher expression in each cell type formed distinct functional networks including Homeobox transcription factors, extracellular matrix (ECM) related proteins, growth factors, and others. These data show that cell-specific RNA populations are intrinsically more characteristic than the disease peculiarities and that VLDLR may play a role in POP pathogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE267852 | GEO | 2024/05/22

REPOSITORIES: GEO

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Profiles of Pelvic organ prolapse [miRNA-seq]

Project description:Pelvic organ prolapse (POP) affects a large proportion of adult women. With the increase in global population ageing, the prevalence of POP is expected to increase in upcoming decades, which will impose a substantial medical burden. Therefore, suitable therapeutical target is important. However, due to the pathogenesis of POP is still unclear, it leads to the failure of POP repair. Herein, we identified changes in ncRNA, and mRNAs in the anterior vaginal wall and uterosacral ligament in patients with POP, providing new insights into the pathogenesis of POP and new targets for treatment.

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Gene expression profile in pelvic organ prolapse

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

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

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Transcriptomics analysis of gene expression in pelvic organ prolapse and control sample

Project description:Anterior vaginal prolapse, as the most common form of POP, severely affect women’s physical and mental health. However, the cellular profiles of vaginal wall and molecular mechanism in pathological process of POP remain unclear. Here, we built the first single-cell transcriptomic atlas of prolapsed vaginal wall. We further revealed prolapse induced aberrant gene expression and transcriptional regulatory networks in cell-type specific manner in POP. Besides extracellular matrix dysregulation, dysfunction of immune cells and immune response were involved with prolapse occur. Computational prediction demonstrated that the abnormal cell-cell communication patterns present among fibroblasts, smooth muscle cells and macrophages in POP, with interplay in extracellular matrix remodeling and regulation of immune reaction. Taken together, our work provides the ﬁrst comprehensive single-cell transcriptomic atlas for deciphering gene expression landscapes of heterogeneous cell types in prolapsed anterior vaginal wall, broadens our understanding of cell identities and cell-type-speciﬁc gene changes in POP and demonstrated the vital role of enhanced interplay between non-immune cells and immune cells in prolapsed vaginal wall.

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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)

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Metabolomics Study of Serum and Urine Samples Reveals Metabolic Pathways and Biomarkers Associated with Pelvic Organ Prolapse

Project description:Pelvic organ prolapse (POP) is a common medical condition among women and involves complicated diagnostics and controversial surgical management. The exact molecular mechanism underlying POP is poorly understood, especially at the metabolism level. To explore the metabolic mechanism underlying POP and discover potential biomarkers for POP diagnosis, we applied a non-targeted metabolomics approach using ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). Metabolomics study of serum samples from patients with POP (n = 24) and controls (n = 22) revealed a total of 59 metabolites that are significantly different (VIP ≥ 1 and p ≤ 0.05) between the two groups. Between urine samples from POP patients (n = 45) and controls (n = 59), 33 metabolites differed significantly (VIP ≥ 1 and p ≤ 0.05). Metabolic pathways affected by these differentially expressed metabolites were analyzed. In both serum and urine samples, three pathways including arginine biosynthesis and purine metabolism were found to be significantly related to POP. Six metabolites including GPC, 1-methyladenosine, maleic acid, L-pyroglutamic acid, inosine, and citrate are significantly changed (VIP ≥ 1 and p ≤ 0.05) in both serum and urine samples from patients with POP. Receiver operating characteristics (ROC) curve analysis showed that using these six metabolites as a biomarker could distinguish patients with POP from controls with good accuracy in both serum (AUC = 1) and urine samples (AUC = 0.854). Collectively, these results further extended our understanding of key regulatory metabolic pathways involved in the pathophysiology of POP, as well as provided some promising biomarkers for effective POP diagnosis.

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