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

被引：47

作者：

Miyazaki, Kaoru ^{[1
,2
]}

Dyson, Matthew T. ^{[1
]}

Coon, John S., V ^{[1
]}

Furukawa, Yuichi ^{[1
]}

Yilmaz, Bahar D. ^{[1
]}

Maruyama, Tetsuo ^{[2
]}

Bulun, Serdar E. ^{[1
]}

机构：

[1] Northwestern Univ, Feinberg Sch Med, Dept Obstet & Gynecol, Prentice Womens Hosp, 250 E Super St,Room 3-2306, Chicago, IL 60611 USA

[2] Keio Univ, Sch Med, Dept Obstet & Gynecol, Shinjuku Ku, Tokyo 1608582, Japan

来源：

STEM CELL REPORTS | 2018年 / 11卷 / 05期

关键词：

FEMALE REPRODUCTIVE-TRACT; MULLERIAN DUCT; EFFICIENT DIFFERENTIATION; DIRECTED DIFFERENTIATION; INTERMEDIATE MESODERM; KIDNEY DEVELOPMENT; GENE-EXPRESSION; IPS CELLS; HUMAN ES; CANCER;

D O I：

10.1016/j.stemcr.2018.10.002

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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 Mullerian 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.

引用

页码：1136 / 1155

页数：20

共 83 条

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