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

  • Author(s): Yucer, Nur
  • Holzapfel, Marie
  • Jenkins Vogel, Tilley
  • Lenaeus, Lindsay
  • Ornelas, Loren
  • Laury, Anna
  • Sareen, Dhruv
  • Barrett, Robert
  • Karlan, Beth Y
  • Svendsen, Clive N
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587694/
No data is associated with this publication.
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.

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