The role of DNA methylation in human trophoblast differentiation.

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Show simple item record Gamage, Teena en Schierding, William en Hurley, Daniel en Tsai, Peter en Ludgate, Jackie L en Bhoothpur, Chandrakanth en Chamley, Lawrence en Weeks, Robert J en Macaulay, Erin C en James, Joanna en 2020-02-17T22:18:40Z en 2018-01 en
dc.identifier.issn 1559-2294 en
dc.identifier.uri en
dc.description.abstract The placenta is a vital fetal exchange organ connecting mother and baby. Specialised placental epithelial cells, called trophoblasts, are essential for adequate placental function. Trophoblasts transform the maternal vasculature to allow efficient blood flow to the placenta and facilitate adequate nutrient uptake. Placental development is in part regulated by epigenetic mechanisms. However, our understanding of how DNA methylation contributes to human trophoblast differentiation is limited. To better understand how genome-wide methylation differences affect trophoblast differentiation, reduced representation bisulfite sequencing (RRBS) was conducted on four matched sets of trophoblasts; side-population trophoblasts (a candidate human trophoblast stem cell population), cytotrophoblasts (an intermediate progenitor population), and extravillous trophoblasts (EVT, a terminally differentiated population) each isolated from the same first trimester placenta. Each trophoblast population had a distinct methylome. In line with their close differentiation relationship, the methylation profile of side-population trophoblasts was most similar to cytotrophoblasts, whilst EVT had the most distinct methylome. In comparison to mature trophoblast populations, side-population trophoblasts exhibited differential methylation of genes and miRNAs involved in cell cycle regulation, differentiation, and regulation of pluripotency. A combined methylomic and transcriptomic approach was taken to better understand cytotrophoblast differentiation to EVT. This revealed methylation of 41 genes involved in epithelial to mesenchymal transition and metastatic cancer pathways, which likely contributes to the acquisition of an invasive EVT phenotype. However, the methylation status of a gene did not always predict gene expression. Therefore, while CpG methylation plays a role in trophoblast differentiation, it is likely not the only regulatory mechanism involved in this process. en
dc.format.medium Print-Electronic en
dc.language eng en
dc.relation.ispartofseries Epigenetics en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.subject Cells, Cultured en
dc.subject Trophoblasts en
dc.subject Humans en
dc.subject Cell Differentiation en
dc.subject DNA Methylation en
dc.title The role of DNA methylation in human trophoblast differentiation. en
dc.type Journal Article en
dc.identifier.doi 10.1080/15592294.2018.1549462 en
pubs.issue 12 en
pubs.begin-page 1154 en
pubs.volume 13 en
dc.rights.holder Copyright: The author en
pubs.end-page 1173 en
pubs.publication-status Published en
dc.rights.accessrights en
pubs.subtype Research Support, Non-U.S. Gov't en
pubs.subtype Journal Article en
pubs.elements-id 757341 en Liggins Institute en Medical and Health Sciences en Medical Sciences en Physiology Division en School of Medicine en Obstetrics and Gynaecology en
dc.identifier.eissn 1559-2308 en
pubs.record-created-at-source-date 2018-11-27 en
pubs.dimensions-id 30475094 en

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