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

Autor: K. Miyazaki, Bahar D. Yilmaz, Serdar E. Bulun, John S. Coon, Matthew T. Dyson, Tetsuo Maruyama, Yuichi Furukawa
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
induced pluripotent stem cell
Primitive Streak
Induced Pluripotent Stem Cells
Embryoid body
Biology
Biochemistry
Article
Mesoderm
03 medical and health sciences
Endometrium
decidualization
Progesterone receptor
Genetics
medicine
Decidua
Humans
Induced pluripotent stem cell
Mullerian Ducts
Wnt Signaling Pathway
lcsh:QH301-705.5
Cells
Cultured
Progesterone
beta Catenin
lcsh:R5-920
Endometrial cancer
Wnt signaling pathway
Decidualization
Cell Differentiation
Epithelial Cells
Cell Biology
endometrial stromal fibroblast
Fibroblasts
medicine.disease
Coelomic epithelium
3. Good health
progesterone signaling
030104 developmental biology
medicine.anatomical_structure
lcsh:Biology (General)
WNT/CTNNB1 pathway
Cancer research
Female
Bone marrow
Stromal Cells
Transcriptome
lcsh:Medicine (General)
Developmental Biology
Zdroj: Stem Cell Reports, Vol 11, Iss 5, Pp 1136-1155 (2018)
Stem Cell Reports
ISSN: 2213-6711
Popis: Summary 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.
Highlights • 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.
Databáze: OpenAIRE
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