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The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids
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The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids
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Journal Article
The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids
2015
Overview
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.
The mechanisms underlying fallopian tube epithelial renewal are unclear. Here, Kessler
et al.
isolate adult stem cells from the human fallopian tube epithelium and generate 3D organoids from these cells
in vitro
that have a similar architecture to that of the fallopian tube.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/106
/ 14/19
/ 14/28
/ 38/61
/ Adult Stem Cells - metabolism
/ Biology
/ Cilia
/ Epithelial Cells - metabolism
/ Fallopian Tubes - metabolism
/ Female
/ Humanities and Social Sciences
/ Humans
/ Microscopy, Electron, Scanning
/ Microscopy, Electron, Transmission
/ Oligonucleotide Array Sequence Analysis
/ Real-Time Polymerase Chain Reaction
/ Receptors, Notch - metabolism
/ Science
