Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Stem cell reports, 2018-11, Vol.11 (5), p.1136-1155

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. •We developed a molecularly defined system for differentiating hiPSCs to EMSFs•hiPSC-derived EMSFs undergo decidualization in response to hormonal stimulation•D14 embryoid bodies recapitulate the molecular signature of primary EMSFs•The WNT/CTNNB1 pathway is required for induction of EMSF from hiPSCs iPSCs provide a patient-specific source that can be differentiated to various cells types. Here, Serdar Bulun and colleagues successfully directed the differentiation of human iPSCs to endometrial fibroblasts (EMSFs) under molecularly defined culture conditions. Activation of CTNNB1 was essential for the induction of EMSFs. These hiPSC-derived tissues illustrate the potential for iPSC-based endometrial regeneration for future cell-based treatments.