title: The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids.
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.
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Kessler
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Hoffmann
authors.affiliation: Core Facility Microscopy, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Brinkmann
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Thieck
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Susan
authors.initials: S
authors.lastname: Jackisch
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Toelle
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Hilmar
authors.initials: H
authors.lastname: Berger
authors.affiliation: Core Facility Microarray, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Mollenkopf
authors.affiliation: Department of Gynecology, Charité University Medicine, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Mandy
authors.initials: M
authors.lastname: Mangler
authors.affiliation: Department of Gynecology, Charité University Medicine, Campus Virchow, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.affiliation: Department of Gynecology, Charité University Medicine, Campus Virchow, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Fotopoulou
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Thomas F
authors.identifier: http://orcid.org/0000-0002-6120-8679
authors.initials: TF
authors.lastname: Meyer
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002923:Cilia; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005187:Fallopian Tubes / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D020411:Oligonucleotide Array Sequence Analysis; D009924:Organ Culture Techniques; D009940:Organoids / Q000166:cytology / Q000378:metabolism*; D019899:Paracrine Communication; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D051880:Receptors, Notch; D051153:Wnt Proteins