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Single-cell transcriptomic data reveal the increase in extracellular matrix organization and antigen presentation abilities of fibroblasts and smooth muscle cells in patients with pelvic organ prolapse

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Abstract

Introduction and hypothesis

We aimed to explore the cellular properties of fibroblasts and smooth muscle cells (SMCs), the two major cell types of the vagina wall, in pelvic organ prolapse (POP) to improve the knowledge of the underlying molecular mechanisms of POP.

Methods

The single-cell RNA sequencing (scRNA-seq) profile GSE151202 was downloaded from NCBI Gene Expression Omnibus, in which vaginal wall tissues were harvested from patients with anterior vaginal wall prolapse and control subjects respectively. The scRNA-seq data of samples (5 POP and 5 controls) were adopted for analysis. Cluster analysis was performed to identify the cell subclusters. Trajectory analysis was applied to construct the differentiation trajectories of fibroblasts and SMCs. Cellular communication analysis was carried out to explore the ligand–receptor interactions between fibroblasts/SMCs and immune cells.

Results

Ten subclusters were determined in both groups, among which fibroblasts and SMCs were the most abundant cell types. Compared with controls, fibroblasts increased whereas SMCs declined in POP. During the transition of fibroblasts and SMCs from a normal into a disease state, extracellular matrix organization and antigen presentation were heightened. The intercellular communications were altered in POP. Interactions between fibroblasts/SMCs and macrophages/natural killer/T cells were strengthened as more ligand–receptor pairs involved in antigen presentation pathways were gained in POP.

Conclusion

Extracellular matrix organization and antigen presentation abilities of fibroblasts and SMCs were enhanced in POP.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Funding: The project was supported by Natural Science Research Funds of Minhang District, Shanghai ( No.2022MHZ034).

References

  1. Akeel NY, Gurland B, Hull T. Pelvic floor disorders related to urology and gynecology. Fundamentals of anorectal surgery. Cham: Springer; 2019. p. 571–82.

  2. Jelovsek JE, Maher C, Barber MD. Pelvic organ prolapse. Lancet. 2007;369:1027–38.

    Article  PubMed  Google Scholar 

  3. Iglesia C, Smithling KR. Pelvic organ prolapse. Am Fam Physician. 2017;96(3):179–85.

    PubMed  Google Scholar 

  4. Barber MD, Maher C. Epidemiology and outcome assessment of pelvic organ prolapse. Int Urogynecol J. 2013;24(11):1783–90.

    Article  PubMed  Google Scholar 

  5. Weintraub AY, Glinter H, Marcus-Braun N. Narrative review of the epidemiology, diagnosis and pathophysiology of pelvic organ prolapse. Int Braz J Urol. 2019;46:5–14.

    Article  Google Scholar 

  6. Wu JM, Hundley AF, Fulton RG, Myers ER. Forecasting the prevalence of pelvic floor disorders in US women: 2010 to 2050. Obstet Gynecol. 2009;114(6):1278–83.

    Article  PubMed  Google Scholar 

  7. Hendrix SL, Clark A, Nygaard I, Aragaki A, Barnabei V, McTiernan A. Pelvic organ prolapse in the Women's Health Initiative: gravity and gravidity. Am J Obstet Gynecol. 2002;186(6):1160–6.

    Article  PubMed  Google Scholar 

  8. Olsen AL, Smith VJ, Bergstrom JO, Colling JC, Clark AL. Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence. Obstet Gynecol. 1997;89(4):501–6.

    Article  CAS  PubMed  Google Scholar 

  9. Chow D, Rodríguez LV. Epidemiology and prevalence of pelvic organ prolapse. Curr Opin Urol. 2013;23(4):293–8.

    Article  PubMed  Google Scholar 

  10. Kolodziejczyk AA, Kim JK, Svensson V, Marioni JC, Teichmann SA. The technology and biology of single-cell RNA sequencing. Mol Cell. 2015;58(4):610–20.

    Article  CAS  PubMed  Google Scholar 

  11. Li Y, Zhang Q-Y, Sun B-F, et al. Single-cell transcriptome profiling of the vaginal wall in women with severe anterior vaginal prolapse. Nat Commun. 2021;12(1):1–13.

    Google Scholar 

  12. Clark GL, Pokutta-Paskaleva AP, Lawrence DJ, et al. Smooth muscle regional contribution to vaginal wall function. Interface Focus. 2019;9(4):20190025.

    Article  PubMed  PubMed Central  Google Scholar 

  13. De Landsheere L, Munaut C, Nusgens B, et al. Histology of the vaginal wall in women with pelvic organ prolapse: a literature review. Int Urogynecol J. 2013;24:2011–20.

    Article  PubMed  Google Scholar 

  14. Mangiola S, Doyle MA, Papenfuss AT. Interfacing Seurat with the R tidy universe. Bioinformatics. 2021;37(22):4100–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Korsunsky I, Millard N, Fan J, et al. Fast, sensitive and accurate integration of single-cell data with harmony. Nat Methods. 2019;16(12):1289–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. McGinnis CS, Murrow LM, Gartner ZJ. DoubletFinder: doublet detection in single-cell RNA sequencing data using artificial nearest neighbors. Cell Syst. 2019;8(4):329–37.e4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Qiu X, Mao Q, Tang Y, et al. Reversed graph embedding resolves complex single-cell trajectories. Nat Methods. 2017;14(10):979–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Jin S, Guerrero-Juarez CF, Zhang L, et al. Inference and analysis of cell-cell communication using CellChat. Nat Commun. 2021;12(1):1–20.

    Article  Google Scholar 

  19. Badiou W, Granier G, Bousquet P-J, Monrozies X, Mares P, de Tayrac R. Comparative histological analysis of anterior vaginal wall in women with pelvic organ prolapse or control subjects. Pilot Study Int Urogynecol J. 2008;19(5):723–9.

    Article  Google Scholar 

  20. Vetuschi A, D’Alfonso A, Sferra R, et al. Changes in muscularis propria of anterior vaginal wall in women with pelvic organ prolapse. Eur J Histochem. 2016;60(1):2604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Boreham MK, Wai CY, Miller RT, Schaffer JI, Word RA. Morphometric analysis of smooth muscle in the anterior vaginal wall of women with pelvic organ prolapse. Am J Obstet Gynecol. 2002;187(1):56–63.

    Article  PubMed  Google Scholar 

  22. Yucel N, Usta A, Guzin K, et al. Immunohistochemical analysis of connective tissue in patients with pelvic organ prolapse. J Mol Histol. 2013;44(1):97–102.

    Article  CAS  PubMed  Google Scholar 

  23. Yu Q, Vazquez R, Zabadi S, Watson RR, Larson DF. T-lymphocytes mediate left ventricular fibrillar collagen cross-linking and diastolic dysfunction in mice. Matrix Biol. 2010;29(6):511–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

Authors

Contributions

Weimin Fan and DuanQing Wu: concepts, manuscript preparation, manuscript review; Liwen Zhang and Jun Ye: design, data acquisition; Junhua Guan and Ying Yang: data acquisition, data analysis; Xiaohui Mei and Rujun Chen: manuscript editing, manuscript review.

Corresponding authors

Correspondence to Xiaohui Mei or Rujun Chen.

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Weimin Fan and Duanqing Wu should be regarded as co-first authors.

Xiaohui Mei and Rujun Chen are co-corresponding authors.

Supplementary information

Figure S1

Violin plots of marker gene expression across ten cell types. (PNG 362 kb)

High-resolution image (TIF 1032 kb)

Figure S2

Gene ontology biological processes enriched by differentially expressed genes in six fibroblast subclusters. (PNG 504 kb)

High-resolution image (TIF 1864 kb)

Table S1 (TIF 60.2 kb)

Table S2 (TIF 69.6 kb)

Table S3 (TIF 67.8 kb)

Table S4 (TIF 42.1 kb)

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Fan, W., Wu, D., Zhang, L. et al. Single-cell transcriptomic data reveal the increase in extracellular matrix organization and antigen presentation abilities of fibroblasts and smooth muscle cells in patients with pelvic organ prolapse. Int Urogynecol J 34, 2529–2537 (2023). https://doi.org/10.1007/s00192-023-05539-9

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