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

McConkey, Cameron A. and Delorme-Axford, Elizabeth and Nickerson, Cheryl A. and Kim, Kwang Sik and Sadovsky, Yoel and Boyle, Jon P. and Coyne, Carolyn B. (2016) A three-dimensional culture system recapitulates placental syncytiotrophoblast development and microbial resistance. Science Advances, 2 (3). e1501462. ISSN 2375-2548

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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.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
McConkey, Cameron A.
Delorme-Axford, Elizabeth
Nickerson, Cheryl A.
Kim, Kwang Sik
Boyle, Jon
Coyne, Carolyn B.
Date: 2016
Date Type: Publication
Journal or Publication Title: Science Advances
Volume: 2
Number: 3
Publisher: AAAS
Page Range: e1501462
DOI or Unique Handle: 10.1126/sciadv.1501462
Schools and Programs: Dietrich School of Arts and Sciences > Biological Sciences
Refereed: No
ISSN: 2375-2548
Official URL:
Article Type: Research Article
Date Deposited: 19 Jun 2020 13:45
Last Modified: 19 Jun 2020 13:45


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