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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation*
  • Cell Line
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism
  • Epithelium / metabolism
  • Fallopian Tubes / cytology
  • Fallopian Tubes / metabolism
  • Female
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Mesoderm / cytology
  • Mesoderm / metabolism
  • Models, Biological
  • Mucous Membrane / cytology
  • Mucous Membrane / metabolism