Mapping the maternal-fetal interface at a single-cell resolution to interrogate the aetiology of severe pre-eclampsia and identify potential disease

在怀孕期间，母亲和胎儿之间有一个高度协调的对话，这种沟通一旦建立，就可以确保婴儿的正确发育，并使母亲能够容忍她未出生的孩子，并保持健康。一种常见且危险的妊娠并发症是先兆子痫（PE），其中孕妇患上高血压，可导致器官衰竭。不幸的是，没有治疗方法，这种情况的根本原因仍然未知。其他人和我们最近的研究表明，母亲-胎儿界面的免疫反应失调，这会影响胎儿组织如何连接到母体血液系统。因此，我们的目标是研究母亲和她未出生的孩子“胎儿”界面的细胞对话，称为母胎界面（MFI）。MFI由属于母亲和胎儿的不同组织组成，并且包括：母体子宫“子宫”壁、胎盘，其供应胎儿，沿着覆盖子宫壁和胎盘的膜。我们将使用技术，使我们能够以单细胞分辨率询问这些组织中的细胞，识别存在的特定细胞类型，以及它正在制造或发出信号。这些方法可以量化数千个基因在其天然“原始”环境中的表达。严重PE患者（造成最大的临床负担，包括孕产妇和胎儿死亡和残疾）与健康对照组之间的比较将有助于我们检测在病理条件下表达不同的特定基因。这些小组将使我们能够了解所看到的差异以及胎龄如何影响这些变化。有了这些信息，我们将在母体血液样本中寻找这些标记物，旨在开发一种诊断PE的新方法，揭示疾病的原因。这种方法有助于更个性化的治疗形式。我们的研究可能有助于找到这种严重妊娠并发症的治疗方法，并调查是否可以通过更简单的血液检查来确定其存在。

During pregnancy there is a highly coordinated dialogue between mother and fetus and this communication, once established, ensures the correct development of the baby and allows the mother to both tolerate her unborn child, and remain well. A common and dangerous pregnancy complication is pre-eclampsia (PE), where a pregnant woman develops high blood pressure that can lead to organ failure. Unfortunately, there is no treatment available and the underlying cause of this condition remains unknown. Recent research by others and us suggests dysregulation of the immune response at the mother-fetal interface, which affects how fetal tissues connect to the maternal blood system. We therefore aim to study cell dialogue at the interface of the mother and her unborn child 'the fetus' known as the maternal-fetal interface (MFI). The MFI consists of different tissues belonging to both mother and fetus and includes; the maternal uterine 'womb' wall, the placenta, which supplies the fetus, along with the membrane that covers the wall of the womb and placenta. We will use technologies that allow us to interrogate the cells in these tissues at a single cell resolution, identifying both the specific cell type that are present, as well as what it is making or signalling. These approaches allow the quantification of the expression of thousands of genes in their native 'original' context.The comparison between patients with severe PE (which poses the greatest clinical burden including maternal and fetal death and disability) versus healthy controls will help us detect specific genes expressed differently in the pathological condition. The groups will enable us to understand the differences seen and how gestational age affects these changes. With this information, we will look for these markers in maternal blood samples, aiming to develop a new way to diagnose PE, that reveals what is the cause of the disease. This approach lends itself to a more personalised form of treatment. Our research may contribute to finding a treatment for this severe pregnancy complication as well as investigating whether its presence can be identified through a more simple blood test.