Early onset preeclampsia in a model for human placental trophoblast.

dc.contributor.author

Sheridan, Megan A

dc.contributor.author

Yang, Ying

dc.contributor.author

Jain, Ashish

dc.contributor.author

Lyons, Alex S

dc.contributor.author

Yang, Penghua

dc.contributor.author

Brahmasani, Sambasiva R

dc.contributor.author

Dai, Aihua

dc.contributor.author

Tian, Yuchen

dc.contributor.author

Ellersieck, Mark R

dc.contributor.author

Tuteja, Geetu

dc.contributor.author

Schust, Danny J

dc.contributor.author

Schulz, Laura C

dc.contributor.author

Ezashi, Toshihiko

dc.contributor.author

Roberts, R Michael

dc.date.accessioned

2023-06-12T17:32:26Z

dc.date.available

2023-06-12T17:32:26Z

dc.date.issued

2019-03

dc.date.updated

2023-06-12T17:32:23Z

dc.description.abstract

We describe a model for early onset preeclampsia (EOPE) that uses induced pluripotent stem cells (iPSCs) generated from umbilical cords of EOPE and control (CTL) pregnancies. These iPSCs were then converted to placental trophoblast (TB) representative of early pregnancy. Marker gene analysis indicated that both sets of cells differentiated at comparable rates. The cells were tested for parameters disturbed in EOPE, including invasive potential. Under 5% O2, CTL TB and EOPE TB lines did not differ, but, under hyperoxia (20% O2), invasiveness of EOPE TB was reduced. RNA sequencing analysis disclosed no consistent differences in expression of individual genes between EOPE TB and CTL TB under 20% O2, but, a weighted correlation network analysis revealed two gene modules (CTL4 and CTL9) that, in CTL TB, were significantly linked to extent of TB invasion. CTL9, which was positively correlated with 20% O2 (P = 0.02) and negatively correlated with invasion (P = 0.03), was enriched for gene ontology terms relating to cell adhesion and migration, angiogenesis, preeclampsia, and stress. Two EOPE TB modules, EOPE1 and EOPE2, also correlated positively and negatively, respectively, with 20% O2 conditions, but only weakly with invasion; they largely contained the same sets of genes present in modules CTL4 and CTL9. Our experiments suggest that, in EOPE, the initial step precipitating disease is a reduced capacity of placental TB to invade caused by a dysregulation of O2 response mechanisms and that EOPE is a syndrome, in which unbalanced expression of various combinations of genes affecting TB invasion provoke disease onset.

dc.identifier

1816150116

dc.identifier.issn

0027-8424

dc.identifier.issn

1091-6490

dc.identifier.uri

https://hdl.handle.net/10161/27908

dc.language

eng

dc.publisher

Proceedings of the National Academy of Sciences

dc.relation.ispartof

Proceedings of the National Academy of Sciences of the United States of America

dc.relation.isversionof

10.1073/pnas.1816150116

dc.subject

Trophoblasts

dc.subject

Placenta

dc.subject

Humans

dc.subject

Pre-Eclampsia

dc.subject

Oxygen

dc.subject

Membrane Transport Proteins

dc.subject

Gene Expression Profiling

dc.subject

Cell Adhesion

dc.subject

Cell Movement

dc.subject

Gene Expression Regulation

dc.subject

Oxidative Stress

dc.subject

Pregnancy

dc.subject

Female

dc.subject

Bone Morphogenetic Protein 4

dc.subject

Induced Pluripotent Stem Cells

dc.subject

Transcriptome

dc.subject

Gene Ontology

dc.title

Early onset preeclampsia in a model for human placental trophoblast.

dc.type

Journal article

duke.contributor.orcid

Schust, Danny J|0000-0003-4561-7808

pubs.begin-page

4336

pubs.end-page

4345

pubs.issue

10

pubs.organisational-group

Duke

pubs.organisational-group

School of Medicine

pubs.organisational-group

Clinical Science Departments

pubs.organisational-group

Obstetrics and Gynecology

pubs.organisational-group

Obstetrics and Gynecology, Reproductive Endocrinology & Fertility

pubs.publication-status

Published

pubs.volume

116

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Early onset preeclampsia in a model for human placental trophoblast.pdf
Size:
1.34 MB
Format:
Adobe Portable Document Format