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

Mirjana Kessler, Karen Hoffmann, Volker Brinkmann, Oliver Thieck, Susan Jackisch, Benjamin Toelle, Hilmar Berger, Hans-Joachim Mollenkopf, Mandy Mangler, Jalid Sehouli, Christina Fotopoulou and Thomas F. Meyer ()
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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
Thomas F. Meyer: Max Planck Institute for Infection Biology

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9989

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