The maternal-fetal interface of successful pregnancies and impact of fetal sex using single cell sequencing
Tania L. Gonzalez,
Ekaterina L Clark,
Barry R. Stripp,
S. Ananth Karumanchi,
Alexander F. Koeppel,
Stephen D. Turner,
Charles R. Farber,
Stephen S Rich,
Erica T Wang,
Margareta D. Pisarska
Posted 18 May 2019
bioRxiv DOI: 10.1101/641118
Posted 18 May 2019
The first trimester is a critical window of maternal-fetal communication for pregnancy. Therefore, we characterized crosstalk in ongoing human pregnancies at 11-13 weeks gestation. RNA-sequencing of matched maternal decidua and placenta identified 818 receptors and 3502 ligands, including 126 differentially expressed receptor-ligand pairs. Using single cell RNA-sequencing to further dissect placenta heterogeneity, we identified five major cell types (trophoblasts, stromal cells, hofbauer cells, antigen presenting cells and endothelial cells) with unique crosstalk at the maternal-fetal interface. We identified seven unique trophoblast subclusters, including new subtypes that transition into the terminal cell types, extra-villous trophoblasts and syncytiotrophoblasts. As fetal sex impacts pregnancy, we analyzed sex differences in each cell type and identified differences in immune cell function. TGFβ1, β-estradiol, and dihydrotestosterone emerge as upstream regulators of sexually dimorphic genes in a cell type specific manner. Thus, the fetal contribution at the maternal-fetal interface is cell and sex specific.
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