MOLECULAR CONTROL OF HAEMOGENIC ENDOTHELIUM FATE

造血内皮命运的分子控制

• 批准号: BB/R007209/1
• 负责人: Valerie Kouskoff
• 金额: $ 67.54万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR007209%2F1
• 关键词: MOLECULAR; CONTROL; HAEMOGENIC; ENDOTHELIUM; FATE

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.

在胚胎生命期间，血液系统是从专门的内皮细胞亚群连续波建立的。从这些内皮细胞亚群中产生血细胞的过程是经过精心安排和协调的，以向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。在本项目中，我们的目标是确定控制这些内皮细胞亚群如何暂时维持或如何受外部刺激指示生成血细胞的潜在分子机制。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控制血液程序。我们假设这两种基因表达调节因子之间的相互作用对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，我们将使用一种基于小鼠胚胎干细胞的实验系统，该系统模拟体外正常发育，并且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。使用荧光报告蛋白，我们将遵循这两个转录调节因子的表达，我们还将确定这两个调节因子如何相互作用。我们的工作将回答一些关于在胚胎发育过程中如何在分子水平上控制血细胞出现的基本问题。

项目成果

The RUNX1b Isoform Defines Hemogenic Competency in Developing Human Endothelial Cells.

• DOI: 10.3389/fcell.2021.812639
• 发表时间: 2021
• 期刊: Frontiers in cell and developmental biology
• 影响因子: 5.5
• 作者: Menegatti S;Potts B;Garcia-Alegria E;Paredes R;Lie-A-Ling M;Lacaud G;Kouskoff V
• 通讯作者: Kouskoff V

Single-cell transcriptomics reveal the dynamic of haematopoietic stem cell production in the aorta.

单细胞转录组学揭示了主动脉中造血干细胞产生的动态。

• DOI: 10.1038/s41467-018-04893-3
• 发表时间: 2018-06-28
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Baron CS;Kester L;Klaus A;Boisset JC;Thambyrajah R;Yvernogeau L;Kouskoff V;Lacaud G;van Oudenaarden A;Robin C
• 通讯作者: Robin C