Characterization of Cell-Subpopulations in the preeclamptic placenta and decidua

• Applicant: Privatdozent Dr. Florian Herse
• Subject Area: Gynaecology and Obstetrics ; Reproductive Medicine, Urology
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 400568798

Preeclampsia (PE) is a pregnancy disorder manifested by a sudden increase in blood pressure, accompanied by a Proteinuria. PE is the leading cause of maternal and fetal morbidity and mortality and a risk factor for developing cardiovascular diseases in later life. Overall, 5-10% of all pregnancies worldwide develop PE. The placenta is a unique temporary organ, which acts as lungs, liver, gut, kidneys and endocrine glands for the fetus, supplying it with nutrients and oxygen, and harmonizes the cross-talk between the fetal and maternal immune system. The structure of the maternal-fetal interface Features a complex relationship between fetal cells and maternal tissue and dysfunctions causes severe consequence for mother and child. It is essential to understand placenta biology on a cellular level, which is now possible with the development of new promising single-cell sequencing technology. Single cell sequencing examines the sequence information from individual cells with optimized next generation sequencing (NGS) technologies. The development of this technology led to the construction of the Human Cell Atlas (HCA) initiative, which aims to create whole-organism tissue maps at the single-cell level. With the previous grant HE6249/7-1 we were fundedfor the “Characterization of Trophoblast-Subpopulations in first trimester placenta”. With the help of the DFG we were able to analyze first trimester villi and decidua and now can present a cell map of the uteroplacental unit in the first trimester of pregnancy. Within thisrenewal proposal here, we apply for funding for the “Characterization of Cell-Subpopulations in the preeclamptic placenta and decidua” by single cell sequencing. We will investigate cells from control and preeclamptic placenta and decidua and will combine the results withthe data from the first trimester samples. This approach will give insights in the developing process of the placenta and in mechanisms leading to preeclampsia. Our global hypothesis is that the cell subpopulations underlie a faulty differentiation process in thepreeclamptic uteroplacental unit compared to uneventful pregnancies. To achieve our goal we will utilize number of novel computational methods: clustering techniques, ontology based molecular signature inference, reconstruction of gene regulatory networks, spatial cell localization, continuum cell cycle analysis and integrative single-cell methods. Specifically, we will pursue the following objectives: Objective 1: Cell sub-populations analysis will reveal differences between the preeclamptic and control placenta/decidua Objective 2:Pseudotime analysis will reveal differentiation processes between the first trimester and term placenta/decidua and are disturbed in preeclampsia.

• DFG Programme: Research Grants