Single-cell transcriptome profiling of the vaginal wall in women with severe anterior vaginal prolapse

Yaqian Li,Ye Zhang,Yidi Ma,Zhijing Sun,Congcong Ma,Yun-Gui Yang,Bao-Fa Sun,Lan Zhu,Honghui Shi,Qing-Yang Zhang,Min Wang,Juan Chen

doi:10.1038/s41467-020-20358-y

Abstract

Anterior vaginal prolapse (AVP) is the most common form of pelvic organ prolapse (POP) and has deleterious effects on women’s health. Despite recent advances in AVP diagnosis and treatment, a cell atlas of the vaginal wall in AVP has not been constructed. Here, we employ single-cell RNA-seq to construct a transcriptomic atlas of 81,026 individual cells in the vaginal wall from AVP and control samples and identify 11 cell types. We reveal aberrant gene expression in diverse cell types in AVP. Extracellular matrix (ECM) dysregulation and immune reactions involvement are identified in both non-immune and immune cell types. In addition, we find that several transcription factors associated with ECM and immune regulation are activated in AVP. Furthermore, we reveal dysregulated cell–cell communication patterns in AVP. Taken together, this work provides a valuable resource for deciphering the cellular heterogeneity and the molecular mechanisms underlying severe AVP.

Highlights

Anterior vaginal prolapse (AVP) is the most common form of pelvic organ prolapse (POP) and has deleterious effects on women’s health
The results indicated that cornification and epidermal cell differentiation were activated in POP, whereas the genes downregulated in POP were mainly enriched in cell chemotaxis, leukocyte migration, and so on
These data were consistent with those in previous reports indicating that immune cells participate in complicated interplay with non-immune cells and the Extracellular matrix (ECM) upon tissue injury[34,35]. These studies did not examine the prolapsed vaginal wall or suggest the vital role of the immune response in the prolapse process. These results indicate that most cell types participate in ECM dysregulation and immune reaction disorder in the prolapsed vaginal wall during the prolapse process

Summary

Introduction

Anterior vaginal prolapse (AVP) is the most common form of pelvic organ prolapse (POP) and has deleterious effects on women’s health. Histological and biochemical alterations in the vaginal wall have been widely studied, revealing that the main constituents in vaginal connective tissues—collagen and elastin fibers—are altered and that an imbalance in matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) leads to dysregulation of extracellular matrix (ECM) metabolism, which in turn influences the architectural remodeling of the vaginal muscularis propria[9] These findings have been identified mainly by immunohistochemistry and western blotting and only partially represent the changes in the vaginal wall in POP. To understand the molecular mechanism underlying the prolapse process, it is important to investigate the cellular composition and cell typespecific changes in gene expression in normal and prolapsed vaginal walls. Our work provides a comprehensive understanding of the molecular mechanism of prolapse at the single-cell level and enhances the understanding of the pathophysiological process of severe AVP, which offers insights for improving current preventative and therapeutic strategies of this disorder

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Results

Conclusion