WNT signalling in human trophectoderm development

人类滋养外胚层发育中的 WNT 信号传导

• 批准号: MR/W006693/1
• 负责人: Norah Fogarty
• 金额: $ 146.19万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW006693%2F1
• 关键词: WNT; signalling; human; trophectoderm; development

I seek to discover the processes that underlie early placenta development. We know that the correct functioning of the placenta is crucial for both mother and baby. After a human egg is fertilised, the cells multiply as the embryo grows. After five days the embryo is called a blastocyst and is made up of around 100 cells. Around 90% of these cells, called trophectoderm cells, will go on to form the trophoblast cells in the placenta. Early pregnancy is often described as a "black box," and due to the difficulties accessing the developing conceptus, we know very little about the key genes and signalling pathways that control the development of the trophectoderm and trophoblast. However, advances in human embryo research and the in vitro models we have to study trophoblast now open up the opportunity to investigate early placenta development. The aim of my research is to identify signalling pathways that are essential for placenta development. From my studies in the human blastocyst, I have identified a pathway called the "WNT signalling pathway" that I hypothesise controls the maturation of trophectoderm into trophoblast. I will test this hypothesis by using advanced imaging techniques to confirm that WNT signalling is active in the embryo. I will investigate the role of this pathway by blocking its activity using precise molecular tools and examining its effect on cell proliferation and gene expression. As human embryos are a limited resource, I will take advantage of in vitro models to refine the molecular tools and techniques I will use to study WNT signalling before applying them to embryos. This approach has the added advantage of deepening our understanding of the relationship between the models and the cell types they represent. These studies will yield novel insights into early human placenta development. In turn, if we understand how these processes work in healthy pregnancies we can begin to understand what defects may underlie complications of pregnancy. This knowledge could inform the understanding and treatment of infertility and placenta diseases such as preeclampsia, miscarriage, and stillbirth.

我试图发现早期胎盘发育的过程。我们知道胎盘的正常功能对母亲和婴儿都至关重要。人类卵子受精后，细胞随着胚胎的生长而繁殖。五天后，胚胎被称为囊胚，由大约 100 个细胞组成。这些细胞中大约 90%（称为滋养外胚层细胞）将继续在胎盘中形成滋养层细胞。怀孕早期通常被描述为一个“黑匣子”，由于难以接近发育中的概念，我们对控制滋养外胚层和滋养层发育的关键基因和信号通路知之甚少。然而，人类胚胎研究的进展和我们必须研究滋养层的体外模型现在为研究早期胎盘发育提供了机会。我的研究目的是确定胎盘发育所必需的信号通路。通过对人类囊胚的研究，我发现了一条称为“WNT 信号通路”的通路，我假设该通路控制滋养外胚层向滋养层的成熟。我将通过使用先进的成像技术来验证这一假设，以确认 WNT 信号在胚胎中是否活跃。我将通过使用精确的分子工具阻断其活性并检查其对细胞增殖和基因表达的影响来研究该途径的作用。由于人类胚胎资源有限，我将利用体外模型来完善我将用于研究 WNT 信号传导的分子工具和技术，然后再将其应用于胚胎。这种方法的另一个优点是加深我们对模型与其所代表的细胞类型之间关系的理解。这些研究将为人类早期胎盘发育提供新的见解。反过来，如果我们了解这些过程如何在健康怀孕中发挥作用，我们就可以开始了解哪些缺陷可能是怀孕并发症的根源。这些知识可以帮助理解和治疗不孕症和胎盘疾病，如先兆子痫、流产和死产。