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    Early onset preeclampsia in a model for human placental trophoblast

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    Author
    Sheridan, M.A.
    Yang, Y.
    Jain, A.
    Date
    2019
    Journal
    Proceedings of the National Academy of Sciences of the United States of America
    Publisher
    National Academy of Sciences
    Type
    Article
    
    Metadata
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    See at
    https://dx.doi.org/10.1073/pnas.1816150116
    Abstract
    We describe a model for early onset preeclampsia (EOPE) that uses induced pluripotent stem cells (iPSCs) generated from umbilical cords of EOPE and control (CTL) pregnancies. These iPSCs were then converted to placental trophoblast (TB) representative of early pregnancy. Marker gene analysis indicated that both sets of cells differentiated at comparable rates. The cells were tested for parameters disturbed in EOPE, including invasive potential. Under 5% O 2 , CTL TB and EOPE TB lines did not differ, but, under hyperoxia (20% O 2 ), invasiveness of EOPE TB was reduced. RNA sequencing analysis disclosed no consistent differences in expression of individual genes between EOPE TB and CTL TB under 20% O 2 , but, a weighted correlation network analysis revealed two gene modules (CTL4 and CTL9) that, in CTL TB, were significantly linked to extent of TB invasion. CTL9, which was positively correlated with 20% O 2 (P = 0.02) and negatively correlated with invasion (P = 0.03), was enriched for gene ontology terms relating to cell adhesion and migration, angiogenesis, preeclampsia, and stress. Two EOPE TB modules, EOPE1 and EOPE2, also correlated positively and negatively, respectively, with 20% O 2 conditions, but only weakly with invasion; they largely contained the same sets of genes present in modules CTL4 and CTL9. Our experiments suggest that, in EOPE, the initial step precipitating disease is a reduced capacity of placental TB to invade caused by a dysregulation of O 2 response mechanisms and that EOPE is a syndrome, in which unbalanced expression of various combinations of genes affecting TB invasion provoke disease onset. Copyright 2019 National Academy of Sciences. All Rights Reserved.
    Keyword
    bone morphogenetic protein-4
    cell migration
    Induced Pluripotent Stem Cells
    Oxidative Stress
    Transcriptome
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062679596&doi=10.1073%2fpnas.1816150116&partnerID=40&md5=0338735988035e7cc713620ffa3c880f; http://hdl.handle.net/10713/8695
    ae974a485f413a2113503eed53cd6c53
    10.1073/pnas.1816150116
    Scopus Count
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