Differentiation of Human Induced Pluripotent Stem Cells to Hormone-Responsive Organoids Resembling Endometrial Cells

Project: Research project

Project Details

Description

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.
StatusActive
Effective start/end date9/1/208/31/21

Funding

  • Friends of Prentice (#1 – FY19)

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