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Nat Commun. 2015 Dec 8;6:8989. doi: 10.1038/ncomms9989.

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

Author information

1
Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
2
Core Facility Microscopy, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
3
Core Facility Microarray, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
4
Department of Gynecology, Charité University Medicine, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.
5
Department of Gynecology, Charité University Medicine, Campus Virchow, Augustenburger Platz 1, 13353 Berlin, Germany.

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.

PMID:
26643275
PMCID:
PMC4686873
DOI:
10.1038/ncomms9989
[Indexed for MEDLINE]
Free PMC Article

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