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iPSC-based modeling of preeclampsia identifies epigenetic defects in extravillous trophoblast differentiation.
Morey, Robert; Bui, Tony; Cheung, Virginia Chu; Dong, Chen; Zemke, Joseph E; Requena, Daniela; Arora, Harneet; Jackson, Madeline G; Pizzo, Donald; Theunissen, Thorold W; Horii, Mariko.
Afiliación
  • Morey R; Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA.
  • Bui T; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Cheung VC; Center for Perinatal Discovery, University of California San Diego, La Jolla, CA 92093, USA.
  • Dong C; Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA.
  • Zemke JE; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Requena D; Center for Perinatal Discovery, University of California San Diego, La Jolla, CA 92093, USA.
  • Arora H; Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA.
  • Jackson MG; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Pizzo D; Center for Perinatal Discovery, University of California San Diego, La Jolla, CA 92093, USA.
  • Theunissen TW; Department of Developmental Biology and Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Horii M; Department of Developmental Biology and Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
iScience ; 27(4): 109569, 2024 Apr 19.
Article en En | MEDLINE | ID: mdl-38623329
ABSTRACT
Preeclampsia (PE) is a hypertensive pregnancy disorder with increased risk of maternal and fetal morbidity and mortality. Abnormal extravillous trophoblast (EVT) development and function is considered to be the underlying cause of PE, but has not been previously modeled in vitro. 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos