E-MTAB-7292
Generation of progesterone-responsive endometrial fibroblasts from human induced pluripotent stem cells: role of the WNT/CTNNB1 pathway
Defective endometrial stromal fibroblasts (EMSF) contribute to uterine factor infertility, endometriosis and endometrial cancer. Induced pluripotent stem cells (iPSC) derived from skin or bone marrow biopsies provide a patient-specific source that can be differentiated to various cells types. Replacement of abnormal EMSF is a potential novel therapeutic approach for endometrial disease; however, the methodology or mechanism for differentiating iPSC to EMSF 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 iPSC (hiPSC) through IM, CE and MD to EMSF 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 EMSF before implantation. These hiPSC-derived tissues illustrated the potential for iPSC-based endometrial regeneration for future cell-based treatments.
Defective endometrial stromal fibroblasts (EMSF) contribute to uterine factor infertility, endometriosis and endometrial cancer. Induced pluripotent stem cells (iPSC) derived from skin or bone marrow biopsies provide a patient-specific source that can be differentiated to various cells types. Replacement of abnormal EMSF is a potential novel therapeutic approach for endometrial disease; however, the methodology or mechanism for differentiating iPSC to EMSF 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 iPSC (hiPSC) through IM, CE and MD to EMSF 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 EMSF before implantation. These hiPSC-derived tissues illustrated the potential for iPSC-based endometrial regeneration for future cell-based treatments.