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bioRxiv · 10.1101/641118

The maternal-fetal interface of successful pregnancies and impact of fetal sex using single cell sequencing

Sun, T.·Gonzalez, T. L.·DENG, N.·DiPentino, R.·Clark, E. L.·Lee, B.·Tang, J.·Wang, Y.·Stripp, B. R.·yao, c.·Tseng, H.-R.·Karumanchi, S. A.·Koeppel, A. F.·Turner, S. D.·Farber, C. R.·Rich, S. S.·Wang, E. T.·Williams, J.·Pisarska, M. D.
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Abstract

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. TGF{beta}1, {beta}-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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Sun, T., Gonzalez, T. L., DENG, N., DiPentino, R., Clark, E. L., Lee, B., Tang, J., Wang, Y., Stripp, B. R., yao, c., Tseng, H.-R., Karumanchi, S. A., Koeppel, A. F., Turner, S. D., Farber, C. R., Rich, S. S., Wang, E. T., Williams, J., Pisarska, M. D.. 2019-05-18. The maternal-fetal interface of successful pregnancies and impact of fetal sex using single cell sequencing. https://doi.org/10.1101/641118

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