Generation of Progesterone-Responsive Endometrial Stromal Fibroblasts from Human Induced Pluripotent Stem Cells: Role of the WNT/CTNNB1 Pathway

Kaoru Miyazaki, Matthew T. Dyson, John S. Coon V, Yuichi Furukawa, Bahar D. Yilmaz, Tetsuo Maruyama, Serdar E. Bulun

Research output: Contribution to journalArticle

5 Citations (Scopus)


Defective endometrial stromal fibroblasts (EMSFs) contribute to uterine factor infertility, endometriosis, and endometrial cancer. Induced pluripotent stem cells (iPSCs) derived from skin or bone marrow biopsies provide a patient-specific source that can be differentiated to various cells types. Replacement of abnormal EMSFs is a potential novel therapeutic approach for endometrial disease; however, the methodology or mechanism for differentiating iPSCs to EMSFs is unknown. The uterus differentiates from the intermediate mesoderm (IM) to form coelomic epithelium (CE) followed by the Müllerian duct (MD). Here, we successfully directed the differentiation of human iPSCs (hiPSCs) through IM, CE, and MD to EMSFs under molecularly defined embryoid body culture conditions using specific hormonal treatments. Activation of CTNNB1 was essential for expression of progesterone receptor that mediated the final differentiation step of EMSFs before implantation. These hiPSC-derived tissues illustrate the potential for iPSC-based endometrial regeneration for future cell-based treatments.

Original languageEnglish
Pages (from-to)1136-1155
Number of pages20
JournalStem Cell Reports
Issue number5
Publication statusPublished - 2018 Nov 13



  • decidualization
  • endometrial stromal fibroblast
  • induced pluripotent stem cell
  • progesterone signaling
  • WNT/CTNNB1 pathway

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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