How are enhancers activated during early embryonic stem cell differentiation

我们所有人都发育成包含数百万个细胞的复杂人类，这些细胞来自一个卵子受精产生的单个细胞。为了从这种单一的细胞状态过渡，细胞必须分裂，并最终改变它们的身份，获得特殊的功能。例如，我们需要特定类型的细胞来填充我们的大脑，这个项目将解决创建这些类型细胞的早期步骤。在这种情况下，我们想要了解的一个基本过程是“增强子激活”的机制。增强子是我们基因组中指导基因表达的部分，即将我们的DNA从我们的基因转化为有用的信息，这些信息提供了决定我们细胞结构和功能的构件。重要的是，不同的增强子在不同的细胞类型中是活跃的，从而允许产生不同的基因产物，从而产生一系列替代细胞类型。然而，我们对这些增强子是如何激活的缺乏基本的了解，因此我们不知道决定细胞命运的机制。这个项目旨在弥合我们知识中的这一差距，并研究增强剂是如何被激活的。重要的是，我们的研究将在胚胎干细胞中进行，因此将有助于我们了解如何操纵这些细胞，这在将这些细胞用于再生医学的背景下是重要的。

All of us develop into complex human beings containing millions of cells from a single cell created by fertilization of an egg. To transit from this single cell state, cells must divide and eventually change their identity and gain specialised functions. For example we need specific types of cells to populate our brains, and this project will address the early steps in the creation of these types of cells. One fundamental process that we aim to understand in this context is the mechanism of "enhancer activation". Enhancers are the parts of our genome that direct gene expression ie the conversion of our DNA from our genes into useful information that provides the building blocks that determine the structure and function of our cells. Importantly, different enhancers are active in different cell types, allowing the production of distinct gene products and hence a range of alternative cell types. However, we lack a fundamental understanding of how these enhancers are activated, and hence we do not know the mechanisms determining cell fate. This project aims to bridge this gap in our knowledge and examine how enhancers are activated. Importantly, our studies will be conducted in embryonic stem cells, and hence will contribute to our knowledge of how to manipulate these cells which is important in the context of using these cells in regenerative medicine.