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ScRNA-seq analysis of vaginal wall tissue in pelvic organ prolapse and control sample

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE151192 | GEO | 2020/11/12

REPOSITORIES: GEO

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Project description:The overall purpose of this University of Utah Pelvic Organ Prolapse Disorder Study was to identify and localize predisposition genes contributing to pelvic organ prolapse (POP). POP cases recruited for this study were identified by one of three methods: high-risk POP pedigree cases, POP sister pairs, and surgically-treated POP cases reporting a family history of POP. High-risk POP pedigree cases were identified using the Utah Population Database (UPDB), a genealogy database of residents in Utah that has been linked to diagnostic ICD9 and CPT codes in medical records at the University of Utah and Intermountain Healthcare. We identified families with a significant excess number of POP cases compared to matched population rates and targeted these individuals for recruitment as well as any other POP cases in the family. POP sister pair cases were identified at the University of Utah Urogyncology clinic for women who had undergone POP surgery and also self-reported one or more sisters who were also surgically treated for POP. POP affection status of all sisters was confirmed either by physical examination or by chart review. Surgically treated-POP cases reporting a family history of POP were identified at the University of Utah Urogyncology clinic by self-report of a family history of POP. Efforts were made to recruit other affected family members and confirm affection status. To obtain DNA, subjects provided either a blood specimen or saliva. Medical records were reviewed by a urogynecologist and diagnostic information for pelvic organ prolapse and stress and overactive bladder were obtained. Collected DNA was genotyped and analyzed. To maintain confidentiality of the familial data, genetic data from only one subject per family has been submitted to dbGaP. Use of the University of Utah Pelvic Organ Prolapse Disorder Study data is limited to investigators studying pelvic floor disorders. These pelvic floor disorders include pelvic organ prolapse, urinary and anal incontinence, and other conditions related to weakening or injury to the muscles and connective tissue in the pelvis as a result of pelvic surgery, pregnancy, or vaginal delivery of a child. These data will be used only for research purposes related to pelvic floor disorders. They will not be used to determine the individual identity of any person or their relationship to another person or for research on non-disease traits.

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ScRNA-seq analysis of vaginal wall tissue in pelvic organ prolapse and control sample

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