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Decoding the endometrial niche of Asherman’s Syndrome at single-cell resolution

Author

Listed:
  • Xavier Santamaria

    (Carlos Simon Foundation, INCLIVA Health Research Institute
    Department Ob/Gyn Vall d’Hebron Institut de Recerca)

  • Beatriz Roson

    (Carlos Simon Foundation, INCLIVA Health Research Institute)

  • Raul Perez-Moraga

    (Carlos Simon Foundation, INCLIVA Health Research Institute
    Igenomix R&D)

  • Nandakumar Venkatesan

    (University of Valencia)

  • Maria Pardo-Figuerez

    (Carlos Simon Foundation, INCLIVA Health Research Institute)

  • Javier Gonzalez-Fernandez

    (Carlos Simon Foundation, INCLIVA Health Research Institute)

  • Jaime Llera-Oyola

    (Carlos Simon Foundation, INCLIVA Health Research Institute)

  • Estefania Fernández

    (Carlos Simon Foundation, INCLIVA Health Research Institute)

  • Inmaculada Moreno

    (Carlos Simon Foundation, INCLIVA Health Research Institute)

  • Andres Salumets

    (University of Tartu
    Competence Centre on Health Technologies
    Karolinska Institute and Karolinska University Hospital)

  • Hugo Vankelecom

    (University of Leuven (KU Leuven))

  • Felipe Vilella

    (Carlos Simon Foundation, INCLIVA Health Research Institute)

  • Carlos Simon

    (Carlos Simon Foundation, INCLIVA Health Research Institute
    University of Valencia
    Beth Israel Deaconess Medical Center, Harvard Medical School)

Abstract

Asherman’s Syndrome is characterized by intrauterine adhesions or scarring, which cause infertility, menstrual abnormalities, and recurrent pregnancy loss. The pathophysiology of this syndrome remains unknown, with treatment restricted to recurrent surgical removal of intrauterine scarring, which has limited success. Here, we decode the Asherman’s Syndrome endometrial cell niche by analyzing data from over 200,000 cells with single-cell RNA-sequencing in patients with this condition and through in vitro analyses of Asherman’s Syndrome patient-derived endometrial organoids. Our endometrial atlas highlights the loss of the endometrial epithelium, alterations to epithelial differentiation signaling pathways such as Wnt and Notch, and the appearance of characteristic epithelium expressing secretory leukocyte protease inhibitor during the window of implantation. We describe syndrome-associated alterations in cell-to-cell communication and gene expression profiles that support a dysfunctional pro-fibrotic, pro-inflammatory, and anti-angiogenic environment.

Suggested Citation

  • Xavier Santamaria & Beatriz Roson & Raul Perez-Moraga & Nandakumar Venkatesan & Maria Pardo-Figuerez & Javier Gonzalez-Fernandez & Jaime Llera-Oyola & Estefania Fernández & Inmaculada Moreno & Andres , 2023. "Decoding the endometrial niche of Asherman’s Syndrome at single-cell resolution," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41656-1
    DOI: 10.1038/s41467-023-41656-1
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    References listed on IDEAS

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