TY - JOUR
T1 - Wide-ranging DNA methylation differences of primary trophoblast cell populations and derived cell lines: Implications and opportunities for understanding trophoblast function
AU - Novakovic, Boris
AU - Gordon, Lavinia
AU - Wong, Nicholas
AU - Moffett, Ashley
AU - Manuelpillai, Ursula
AU - Craig, Jeffrey
AU - Sharkey, Andrew
AU - Saffery, Richard
PY - 2011
Y1 - 2011
N2 - 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.
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.
UR - http://www.ncbi.nlm.nih.gov/pubmed/21289002
U2 - 10.1093/molehr/gar005
DO - 10.1093/molehr/gar005
M3 - Article
SN - 1360-9947
VL - 17
SP - 344
EP - 353
JO - Molecular Human Reproduction
JF - Molecular Human Reproduction
IS - 6
ER -