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

4 Citations (Scopus)

Abstract

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
Volume11
Issue number5
DOIs
Publication statusPublished - 2018 Nov 13

Fingerprint

Induced Pluripotent Stem Cells
Fibroblasts
Stem cells
Progesterone
Mesoderm
Ducts
Epithelium
Uterine Diseases
Embryoid Bodies
Biopsy
Progesterone Receptors
Endometriosis
Endometrial Neoplasms
Cell culture
Infertility
Uterus
Regeneration
Skin
Bone
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

Generation of Progesterone-Responsive Endometrial Stromal Fibroblasts from Human Induced Pluripotent Stem Cells : Role of the WNT/CTNNB1 Pathway. / Miyazaki, Kaoru; Dyson, Matthew T.; Coon V, John S.; Furukawa, Yuichi; Yilmaz, Bahar D.; Maruyama, Tetsuo; Bulun, Serdar E.

In: Stem Cell Reports, Vol. 11, No. 5, 13.11.2018, p. 1136-1155.

Research output: Contribution to journalArticle

Miyazaki, Kaoru ; Dyson, Matthew T. ; Coon V, John S. ; Furukawa, Yuichi ; Yilmaz, Bahar D. ; Maruyama, Tetsuo ; Bulun, Serdar E. / Generation of Progesterone-Responsive Endometrial Stromal Fibroblasts from Human Induced Pluripotent Stem Cells : Role of the WNT/CTNNB1 Pathway. In: Stem Cell Reports. 2018 ; Vol. 11, No. 5. pp. 1136-1155.
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