Sci Rep. 2017 Sep 6;7(1):10741. doi: 10.1038/s41598-017-05519-2.

Directed Differentiation of Human Induced Pluripotent Stem Cells into Fallopian Tube Epithelium.

Yucer N^1,2, Holzapfel M², Jenkins Vogel T², Lenaeus L¹, Ornelas L¹, Laury A³, Sareen D¹, Barrett R¹, Karlan BY^4,5, Svendsen CN^6,7.

Abstract

The fallopian tube epithelium (FTE) has been recognized as a site of origin of high-grade serous ovarian cancer (HGSC). However, the absence of relevant in vitro human models that can recapitulate tissue-specific architecture has hindered our understanding of FTE transformation and initiation of HGSC. Here, induced pluripotent stem cells (iPSCs) were used to establish a novel 3-dimensional (3D) human FTE organoid in vitro model containing the relevant cell types of the human fallopian tube as well as a luminal architecture that closely reflects the organization of fallopian tissues in vivo. Modulation of Wnt and BMP signaling directed iPSC differentiation into Müllerian cells and subsequent use of pro-Müllerian growth factors promoted FTE precursors. The expression and localization of Müllerian markers verified correct cellular differentiation. An innovative 3D growth platform, which enabled the FTE organoid to self-organize into a convoluted luminal structure, permitted matured differentiation to a FTE lineage. This powerful human-derived FTE organoid model can be used to study the earliest stages of HGSC development and to identify novel and specific biomarkers of early fallopian tube epithelial cell transformation.