LYVE-1 Hofbauer cells in preeclampsia

先兆子痫（PE）是一种妊娠期疾病，表现为血压突然升高，伴有蛋白尿。PE是孕产妇和胎儿发病和死亡的主要原因，也是晚年发生心血管疾病的危险因素。总的来说，全世界5-10%的妊娠会发生PE。胎盘是一种独特的临时器官，特别是在怀孕早期，它替代胎儿器官，直到它们完全成熟。胎盘的主要功能之一是在母亲和胎儿之间转移几乎所有的营养和气体。此外，胎盘作为内分泌器官，分泌过多的类固醇和蛋白质激素、代谢蛋白、生长因子和细胞因子以使母体生理适应妊娠。母胎界面的结构特征是胎儿细胞和母体组织之间的复杂关系，功能障碍会对母亲和儿童造成严重后果。在细胞水平上了解胎盘生物学是至关重要的，随着新的有前途的单细胞测序技术的发展，这已经成为可能。单细胞测序（scRNA-seq）通过优化的下一代测序（NGS）技术检查来自单个细胞的序列信息。这项技术的发展导致了人类细胞图谱（HCA）计划的建立，该计划旨在在单细胞水平上创建全生物体组织图谱。通过我们之前的双边联合项目，由奥地利科学基金（FWF资助I 3304，Gauster）和德国研究共同体（DFG资助HE 6249/5-1，Herse）资助，我们能够研究血管紧张素II对胎盘fractalkine的作用。在本文的后续提案中，我们申请资金用于检查“先兆子痫中的LYVE-1+霍夫鲍尔细胞”。通过使用我们目前的scRNA-seq数据和先进的空间转录组学以及验证分子技术和原代细胞和组织的功能测定的计算方法，我们将研究LYVE 1+ Hofbauer细胞群在血管周围基质稳态/重塑中的作用及其对胎儿-胎盘血管功能的潜在影响。这种方法将提供新的见解异常发育过程中的胎盘及其巨噬细胞导致PE。

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.