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

研究成果: Article査読

34 被引用数 (Scopus)

抄録

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. 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.

本文言語English
ページ(範囲)1136-1155
ページ数20
ジャーナルStem cell reports
11
5
DOI
出版ステータスPublished - 2018 11月 13

ASJC Scopus subject areas

  • 生化学
  • 遺伝学
  • 発生生物学
  • 細胞生物学

フィンガープリント

「Generation of Progesterone-Responsive Endometrial Stromal Fibroblasts from Human Induced Pluripotent Stem Cells: Role of the WNT/CTNNB1 Pathway」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル