Wide-ranging DNA methylation differences of primary trophoblast cell populations and derived cell lines: Implications and opportunities for understanding trophoblast function

Boris Novakovic, Lavinia Gordon, Nicholas Wong, Ashley Moffett, Ursula Manuelpillai, Jeffrey Craig, Andrew Sharkey, Richard Saffery

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Difficulties associated with long-term culture of primary trophoblasts have proven to be a major hurdle in their functional characterization. In order to circumvent this issue, several model cell lines have been established over many years using a variety of different approaches. Due to their differing origins, gene expression profiles and behaviour in vitro, different model lines have been utilized to investigate specific aspects of trophoblast biology. However, generally speaking, the molecular mechanisms underlying functional differences remain unclear. In this study, we profiled genome-scale DNA methylation in primary first trimester trophoblast cells and seven commonly used trophoblast-derived cell lines in an attempt to identify functional pathways differentially regulated by epigenetic modification in these cells. We identified a general increase in DNA promoter methylation levels in four choriocarcinoma (CCA)-derived lines and transformed HTR-8/SVneo cells, including hypermethylation of several genes regularly seen in human cancers, while other differences in methylation were noted in genes linked to immune responsiveness, cell morphology, development and migration across the different cell populations.
    Original languageEnglish
    Pages (from-to)344 - 353
    Number of pages10
    JournalMolecular Human Reproduction
    Volume17
    Issue number6
    DOIs
    Publication statusPublished - 2011

    Cite this

    Novakovic, Boris ; Gordon, Lavinia ; Wong, Nicholas ; Moffett, Ashley ; Manuelpillai, Ursula ; Craig, Jeffrey ; Sharkey, Andrew ; Saffery, Richard. / Wide-ranging DNA methylation differences of primary trophoblast cell populations and derived cell lines: Implications and opportunities for understanding trophoblast function. In: Molecular Human Reproduction. 2011 ; Vol. 17, No. 6. pp. 344 - 353.
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    abstract = "Difficulties associated with long-term culture of primary trophoblasts have proven to be a major hurdle in their functional characterization. In order to circumvent this issue, several model cell lines have been established over many years using a variety of different approaches. Due to their differing origins, gene expression profiles and behaviour in vitro, different model lines have been utilized to investigate specific aspects of trophoblast biology. However, generally speaking, the molecular mechanisms underlying functional differences remain unclear. In this study, we profiled genome-scale DNA methylation in primary first trimester trophoblast cells and seven commonly used trophoblast-derived cell lines in an attempt to identify functional pathways differentially regulated by epigenetic modification in these cells. We identified a general increase in DNA promoter methylation levels in four choriocarcinoma (CCA)-derived lines and transformed HTR-8/SVneo cells, including hypermethylation of several genes regularly seen in human cancers, while other differences in methylation were noted in genes linked to immune responsiveness, cell morphology, development and migration across the different cell populations.",
    author = "Boris Novakovic and Lavinia Gordon and Nicholas Wong and Ashley Moffett and Ursula Manuelpillai and Jeffrey Craig and Andrew Sharkey and Richard Saffery",
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    Wide-ranging DNA methylation differences of primary trophoblast cell populations and derived cell lines: Implications and opportunities for understanding trophoblast function. / Novakovic, Boris; Gordon, Lavinia; Wong, Nicholas; Moffett, Ashley; Manuelpillai, Ursula; Craig, Jeffrey; Sharkey, Andrew; Saffery, Richard.

    In: Molecular Human Reproduction, Vol. 17, No. 6, 2011, p. 344 - 353.

    Research output: Contribution to journalArticleResearchpeer-review

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    AU - Novakovic, Boris

    AU - Gordon, Lavinia

    AU - Wong, Nicholas

    AU - Moffett, Ashley

    AU - Manuelpillai, Ursula

    AU - Craig, Jeffrey

    AU - Sharkey, Andrew

    AU - Saffery, Richard

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    AB - Difficulties associated with long-term culture of primary trophoblasts have proven to be a major hurdle in their functional characterization. In order to circumvent this issue, several model cell lines have been established over many years using a variety of different approaches. Due to their differing origins, gene expression profiles and behaviour in vitro, different model lines have been utilized to investigate specific aspects of trophoblast biology. However, generally speaking, the molecular mechanisms underlying functional differences remain unclear. In this study, we profiled genome-scale DNA methylation in primary first trimester trophoblast cells and seven commonly used trophoblast-derived cell lines in an attempt to identify functional pathways differentially regulated by epigenetic modification in these cells. We identified a general increase in DNA promoter methylation levels in four choriocarcinoma (CCA)-derived lines and transformed HTR-8/SVneo cells, including hypermethylation of several genes regularly seen in human cancers, while other differences in methylation were noted in genes linked to immune responsiveness, cell morphology, development and migration across the different cell populations.

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