LYVE-1 Hofbauer cells in preeclampsia

• Applicant: Privatdozent Dr. Florian Herse
• Subject Area: Gynaecology and Obstetrics ; Reproductive Medicine, Urology
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 327245046

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 especially in the early stages of pregnancy substitutes fetal organs until they reach full maturity. One of the key functions of the placenta is the transfer of almost all nutrients and gases between mother and fetus. Moreover, the placenta acts as an endocrine organ, secreting a plethora of steroid and protein hormones, metabolic proteins, growth factors, and cytokines to adapt maternal physiology to pregnancy. The structure of the maternal-fetal interface features a complex relationship between fetal cells and maternal tissue and dysfunctions cause severe consequences for mother and child. It is essential to understand the placenta biology on a cellular level, which has now become possible with the development of new promising single-cell sequencing technology. Single cell sequencing (scRNA-seq) 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 our previous bilateral joint project, funded by the Austrian Science Fund (FWF grant I 3304, Gauster) and the Deutsche Forschungsgemeinschaft (DFG grant HE6249/5-1, Herse), we were able to study the role of angiotensin II on placental fractalkine. Within this follow-up proposal here, we apply for funding for examination of the “LYVE-1+ Hofbauer cells in preeclampsia”. By computational approaches using our current scRNA-seq data and progressing spatial transcriptomics as well as validating molecular techniques and functional assays with primary cells and tissue, we will investigate the role of the LYVE 1+ Hofbauer cell population in perivascular matrix homeostasis/remodeling and its potential consequence on fetal-placental blood vessel function. This approach will give novel insights in the aberrant developmental processes of the placenta and its macrophages leading to PE.

• DFG Programme: Research Grants
• International Connection: Austria
• Cooperation Partner: Professor Martin Gauster, Ph.D.