iPSC-based modeling of preeclampsia identifies epigenetic defects in extravillous trophoblast differentiation
Robert Morey, Tony Bui, Virginia Chu Cheung, Chen Dong, Joseph E. Zemke, Daniela F. Requena, Harneet Arora, Madeline G. Jackson, Donald Pizzo, Thorold W. Theunissen, Mariko Horii
Abstract
. We previously derived induced pluripotent stem cells (iPSCs) from placentas of PE patients and characterized abnormalities in formation of syncytiotrophoblast and responses to changes in oxygen tension. In this study, we converted these primed iPSC to naïve iPSC, and then derived trophoblast stem cells (TSCs) and EVT to evaluate molecular mechanisms underlying PE. We found that primed (but not naïve) iPSC-derived PE-EVT have reduced surface HLA-G, blunted invasive capacity, and altered EVT-specific gene expression. These abnormalities correlated with promoter hypermethylation of genes associated with the epithelial-mesenchymal transition pathway, specifically in primed-iPSC derived PE-EVT. Our findings indicate that abnormal epigenetic regulation might play a role in PE pathogenesis.