MOLECULAR CONTROL OF HAEMOGENIC ENDOTHELIUM FATE

在胚胎时期，血液系统是由专门的内皮亚群在连续的波中建立的。这些内皮亚群产生的血细胞是经过精心安排和协调的，以便为生长中的胚胎提供每个连续发育阶段所需的特定血细胞类型。调控这些特化内皮细胞亚群何时产生血细胞的分子机制尚不清楚。在目前的项目中，我们的目标是确定潜在的分子机制，控制这些内皮亚群是如何暂时维持的，或者它们是如何被外部刺激指示产生血细胞的。在这种情况下，我们将探讨两个转录调节因子之间的相互作用，一个控制内皮程序和一个控制血液程序。我们假设这两个基因表达调节因子之间的相互作用对于控制胚胎发育过程中血细胞生成的时间至关重要。为了解决这些问题，我们将使用一个基于小鼠胚胎干细胞的实验系统，该系统可以在体外模拟正常发育，我们可以很容易地操纵基因表达并产生足够的细胞来检查许多不同的特征。利用荧光报告蛋白，我们将跟踪这两种转录调节因子的表达，我们还将确定这两种调节因子如何相互作用。我们的工作将回答一些关于胚胎发育过程中血细胞出现如何在分子水平上受到控制的基本问题。

During embryonic life, the blood system is established in successive waves from specialized endothelial subsets. The generation of blood cells from these endothelial subsets is carefully timed and coordinated to provide the growing embryo with specific blood cell types that are needed at each successive stage of development. The molecular mechanism that regulates when these subsets of specialized endothelial give rise to blood cells is still poorly understood.In the present project, we will aim to determine the underlying molecular mechanism that controls how these endothelium subsets are temporally maintained or how they are instructed by external stimuli to generate blood cells. In this context, we will explore the interaction between two transcriptional regulators, one controlling the endothelial programme and one controlling the blood programme. We hypothesise that the interaction between these two regulators of gene expression is critical to control the timing of blood cell generation during embryonic development. To address these questions, we will use an experimental system based on mouse embryonic stem cells that mimics normal development in vitro and in which we can easily manipulate gene expression and generate enough cells to examine many different features. Using fluorescent reporter proteins, we will follow the expression of these two transcriptional regulators and we will also determine how these two regulators interact with each other. Our work will answer a number of fundamental questions on how blood cell emergence is controlled at the molecular level during embryonic development.