The endometrium is the multilayered mucosa of the uterus that proliferates, differentiates, sheds, and regenerates in response to ovarian steroid hormones. Defective Endometrial stromal cell (ESC) function plays critical roles in the development of endometrial disorders including uterine factor infertility. Cell replacement therapy whereby abnormal ESCs are replaced with normal ESCs can represent a novel therapeutic approach to such endometrial disease. The most reliable source of normal ESCs applicable for clinical use would be from patient-derived induced pluripotent stem cells (iPSCs). We recently developed the protocol to differentiate hiPSCs to ESCs. The objective of this project is to determine the mechanistic role of pathways involved in the differentiation of hiPSCs to ESCs. hiPSCs will be cultured in a medium supplemented with several chemical cocktails containing a WNT/CTNNB1 activator. After 14 days of the treatment, cells express ESC markers including HOXA11 and PGR and undergo decidualization after treating them with progestin, confirmed by upregulation of IGFBP1. Pathway enrichment analysis will be performed based on the transcriptome data to specify pathways essential for induction of ESCs from hiPSCs. We will then add inhibitors of such pathways during differentiation of hiPSCs to confirm how those pathways affect the expression of differentiation markers.
|Effective start/end date||9/1/20 → 8/31/22|
- Friends of Prentice (#1 – FY19)
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