Single cell transcriptional signatures of the human placenta in term and preterm parturition
Abstract
More than 135 million births occur each year; yet, the molecular underpinnings of human parturition in gestational tissues, and in particular the placenta, are still poorly understood. The placenta is a complex heterogeneous organ including cells of both maternal and fetal origin, and insults that disrupt the maternal-fetal dialogue could result in adverse pregnancy outcomes such as preterm birth. There is limited knowledge of the cell type composition and transcriptional activity of the placenta and its compartments during physiologic and pathologic parturition. To fill this knowledge gap, we used scRNA-seq to profile the placental villous tree, basal plate, and chorioamniotic membranes of women with or without labor at term and those with preterm labor. Significant differences in cell type composition and transcriptional profiles were found among placental compartments and across study groups. For the first time, two cell types were identified: 1) lymphatic endothelial decidual cells in the chorioamniotic membranes, and 2) non-proliferative interstitial cytotrophoblasts in the placental villi. Maternal macrophages from the chorioamniotic membranes displayed the largest differences in gene expression (e.g. NFKB1) in both processes of labor; yet, specific gene expression changes were also detected in preterm labor. Importantly, several placental scRNA-seq transcriptional signatures were modulated with advancing gestation in the maternal circulation, and specific immune cell type signatures were increased with labor at term (NK-cell and activated T-cell signatures) and with preterm labor (macrophage, monocyte, and activated T-cell signatures). Herein, we provide a catalogue of cell types and transcriptional profiles in the human placenta, shedding light on the molecular underpinnings and non-invasive prediction of the physiologic and pathologic parturition.
Data availability
Protected Human subjects data deposited in dbGaP phs001886.v1.p1Data from other sources detailed in manuscript
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Genome Scale Analysis of miRNA and mRNA regulation during preterm laborNCBI Gene Expression Omnibus, GSE96083.
Article and author information
Author details
Funding
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HHSN275201300006C)
- Roberto Romero
Wayne State University (Perinatal Research Initiative)
- Nardhy Gomez-Lopez
The funders had no role in study design, data collection and interpretation.
Ethics
Human subjects: The collection and use of human materials for research purposes were approved by the Institutional Review Boards of the Wayne State University School of Medicine 040302M1F. All participating women provided written informed consent prior to sample collection. Data sharing certification (dbGaP phs001886.v1.p1) is attached.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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