Characterization of Cell-Subpopulations in the preeclamptic placenta and decidua

先兆子痫胎盘和蜕膜细胞亚群的特征

• 批准号: 400568798
• 负责人: Privatdozent Dr. Florian Herse
• 金额: --
• 依托单位: Max-Delbrück-Centrum für Molekulare Medizin (MDC) in der Helmholtz-Gemeinschaft
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/400568798?language=en
• 关键词: Characterization; Cell; Subpopulations; preeclamptic; placenta

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.

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是母亲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。胎盘是一个独特的临时器官，它充当胎儿的肺、肝、肠、肾和内分泌腺，为胎儿提供营养和氧气，并协调胎儿和母体免疫系统之间的相互作用。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孩子造成严重后果。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，这一点现在已经成为可能。单细胞测序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。在之前的基金HE 6249/7-1中，我们获得了“早期妊娠胎盘滋养层细胞亚群的特征”的资助。在DFG的帮助下，我们能够分析妊娠早期绒毛和蜕膜，现在可以提供妊娠早期子宫胎盘单位的细胞图。在本更新提案中，我们申请了“通过单细胞测序对先兆子痫胎盘和蜕膜中细胞亚群的表征”的资助。我们将研究来自对照组和先兆子痫患者胎盘和蜕膜的细胞，并将联合收割机的结果与来自妊娠早期样本的数据相结合。这种方法将使人们了解胎盘的发育过程和导致先兆子痫的机制。我们的总体假设是，与正常妊娠相比，先兆子痫子宫胎盘单位的细胞亚群是错误分化过程的基础。为了实现我们的目标，我们将利用一些新的计算方法：聚类技术，基于本体论的分子特征推断，基因调控网络的重建，空间细胞定位，连续体细胞周期分析和综合单细胞方法。具体来说，我们将追求以下目标：目标1：细胞亚群分析将揭示先兆子痫和对照胎盘/蜕膜之间的差异目标2：假时间分析将揭示早期妊娠和足月胎盘/蜕膜之间的分化过程，并在先兆子痫中受到干扰。