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The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids

Author

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  • Mirjana Kessler

    (Max Planck Institute for Infection Biology)

  • Karen Hoffmann

    (Max Planck Institute for Infection Biology)

  • Volker Brinkmann

    (Core Facility Microscopy, Max Planck Institute for Infection Biology)

  • Oliver Thieck

    (Max Planck Institute for Infection Biology)

  • Susan Jackisch

    (Max Planck Institute for Infection Biology)

  • Benjamin Toelle

    (Max Planck Institute for Infection Biology)

  • Hilmar Berger

    (Max Planck Institute for Infection Biology)

  • Hans-Joachim Mollenkopf

    (Core Facility Microarray, Max Planck Institute for Infection Biology)

  • Mandy Mangler

    (Charité University Medicine, Campus Mitte)

  • Jalid Sehouli

    (Charité University Medicine, Campus Virchow)

  • Christina Fotopoulou

    (Charité University Medicine, Campus Virchow
    Present address: Department of Gynaecological Oncology, West London Gynaecological Cancer Centre and Ovarian Cancer Action Research Centre, Imperial College Healthcare Trust London, London W12 0NN, UK)

  • Thomas F. Meyer

    (Max Planck Institute for Infection Biology)

Abstract

The epithelial lining of the fallopian tube is of critical importance for human reproduction and has been implicated as a site of origin of high-grade serous ovarian cancer. Here we report on the establishment of long-term, stable 3D organoid cultures from human fallopian tubes, indicative of the presence of adult stem cells. We show that single epithelial stem cells in vitro can give rise to differentiated organoids containing ciliated and secretory cells. Continuous growth and differentiation of organoids depend on both Wnt and Notch paracrine signalling. Microarray analysis reveals that inhibition of Notch signalling causes downregulation of stem cell-associated genes in parallel with decreased proliferation and increased numbers of ciliated cells and that organoids also respond to oestradiol and progesterone treatment in a physiological manner. Thus, our organoid model provides a much-needed basis for future investigations of signalling routes involved in health and disease of the fallopian tube.

Suggested Citation

  • Mirjana Kessler & Karen Hoffmann & Volker Brinkmann & Oliver Thieck & Susan Jackisch & Benjamin Toelle & Hilmar Berger & Hans-Joachim Mollenkopf & Mandy Mangler & Jalid Sehouli & Christina Fotopoulou , 2015. "The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids," Nature Communications, Nature, vol. 6(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9989
    DOI: 10.1038/ncomms9989
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    Cited by:

    1. Melati S. Abdul Halim & Jennifer M. Dyson & Max M. Gong & Moira K. O’Bryan & Reza Nosrati, 2024. "Fallopian tube rheology regulates epithelial cell differentiation and function to enhance cilia formation and coordination," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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