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Transcriptomic features of trophoblast lineage cells derived from BMP4-treated human induced pluripotent stem cells

ABSTRACT: We explored the trophoblast differentiation model using human induced pluripotent stem cells (hiPSCs) to gain new insights into the early development of human placenta. In our previous study, we have optimized culture conditions for hiPSC-derived trophoblasts. To identify the characteristics of trophoblast lineage cells derived from BMP4-treated hiPSCs, we collected cells using a pan-trophoblast marker, KRT7, with flow cytometry and performed comprehensive gene expression analysis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE124832 | GEO | 2019/01/31

REPOSITORIES: GEO

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Project description: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 behavior 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. Interestingly, CCA-derived lines show an overall methylation profile more similar to unrelated solid cancers than to untransformed trophoblasts, highlighting the role of aberrant DNA methylation in CCA development and/or long term culturing. Comparison of DNA methylation and gene expression in CCA lines and cytotrophoblasts revealed a significant contribution of DNA methylation to overall expression profile. These data highlight the variability in epigenetic state between primary trophoblasts and cell models in pathways underpinning a wide range of cell functions, providing valuable candidate pathways for future functional investigation in different cell populations. This study also confirms the need for caution in the interpretation of data generated from manipulation of such pathways in vitro. Purified primary trophoblast populations and trophoblast-derived cell lines were used

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Transcriptomic features of trophoblast lineage cells derived from BMP4-treated human induced pluripotent stem cells

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