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

TLDR

The fallopian tube epithelium is critical for reproduction and may initiate high‑grade serous ovarian cancer. The study establishes long‑term, stable 3D organoid cultures from human fallopian tubes to demonstrate adult stem cell presence. These cultures were developed as long‑term, stable 3D organoids. Single epithelial stem cells generate organoids containing ciliated and secretory cells, whose growth depends on Wnt and Notch signaling; Notch inhibition downregulates stem‑cell genes, reduces proliferation, increases ciliated cells, and the organoids respond to oestradiol and progesterone, providing a platform for future fallopian tube signaling studies.

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.