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A three-dimensional culture system recapitulates placental syncytiotrophoblast development and microbial resistance.

dc.contributor.author McConkey, Cameron A
dc.contributor.author Delorme-Axford, Elizabeth
dc.contributor.author Nickerson, Cheryl A
dc.contributor.author Kim, Kwang Sik
dc.contributor.author Sadovsky, Yoel
dc.contributor.author Boyle, Jon P
dc.contributor.author Coyne, Carolyn B
dc.date.accessioned 2021-04-16T20:02:01Z
dc.date.available 2021-04-16T20:02:01Z
dc.date.issued 2016-03-04
dc.identifier 1501462
dc.identifier.issn 2375-2548
dc.identifier.issn 2375-2548
dc.identifier.uri https://hdl.handle.net/10161/22590
dc.description.abstract In eutherians, the placenta acts as a barrier and conduit at the maternal-fetal interface. Syncytiotrophoblasts, the multinucleated cells that cover the placental villous tree surfaces of the human placenta, are directly bathed in maternal blood and are formed by the fusion of progenitor cytotrophoblasts that underlie them. Despite their crucial role in fetal protection, many of the events that govern trophoblast fusion and protection from microbial infection are unknown. We describe a three-dimensional (3D)-based culture model using human JEG-3 trophoblast cells that develop syncytiotrophoblast phenotypes when cocultured with human microvascular endothelial cells. JEG-3 cells cultured in this system exhibit enhanced fusogenic activity and morphological and secretory activities strikingly similar to those of primary human syncytiotrophoblasts. RNASeq analyses extend the observed functional similarities to the transcriptome, where we observed significant overlap between syncytiotrophoblast-specific genes and 3D JEG-3 cultures. Furthermore, JEG-3 cells cultured in 3D are resistant to infection by viruses and Toxoplasma gondii, which mimics the high resistance of syncytiotrophoblasts to microbial infections in vivo. Given that this system is genetically manipulatable, it provides a new platform to dissect the mechanisms involved in syncytiotrophoblast development and microbial resistance.
dc.language eng
dc.publisher American Association for the Advancement of Science (AAAS)
dc.relation.ispartof Science advances
dc.relation.isversionof 10.1126/sciadv.1501462
dc.subject Cell Line
dc.subject Trophoblasts
dc.subject Placenta
dc.subject Humans
dc.subject Cell Culture Techniques
dc.subject Gene Expression Profiling
dc.subject Transcription, Genetic
dc.subject Pregnancy
dc.subject Female
dc.title A three-dimensional culture system recapitulates placental syncytiotrophoblast development and microbial resistance.
dc.type Journal article
duke.contributor.id Coyne, Carolyn B|1086848
dc.date.updated 2021-04-16T20:01:59Z
pubs.begin-page e1501462
pubs.issue 3
pubs.organisational-group School of Medicine
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group Duke
pubs.organisational-group Basic Science Departments
pubs.publication-status Published
pubs.volume 2
duke.contributor.orcid Coyne, Carolyn B|0000-0002-1884-6309


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