The role of the transcription factor Sp1 in embryonic macrophage development

转录因子Sp1在胚胎巨噬细胞发育中的作用

• 批准号: G0901579/1
• 负责人: Constanze Bonifer
• 金额: $ 66.9万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0901579%2F1
• 关键词: role; transcription; factor; Sp1; embryonic

Macrophages are a type of white blood cell which are very important for the health of an organism. These cells have the ability to recognize infectious particles and send out alarm signals that mobilize the bodies? defenses. However, in the embryo they have different functions. Here they function mainly as scavengers and have the ability to ?eat? dead cells and cell debris, and therefore play important roles in shaping the body outline. For example, even in mammals hands are originally webbed and macrophages remove the skin between the fingers. In the project described here we wish to address the question how this cell type is formed in the embryo. All different cells of the organism originate from a single egg; the reason why they are all different is that they all express different sets of genes. Therefore we want to know which genes are responsible for generating embryonic macrophages. To find out which genes are responsible, we will use an embryonic stem (ES) cell line that lacks one specific protein (Sp1) that is responsible for the activity of many genes. We found that normal ES cells can be turned into embryonic macrophages by culturing them in special medium. However, in the absence of Sp1 these cells are not formed. When Sp1 is removed in mice, embryos are unable to develop. The reason for this is unclear, but our work suggests that macrophages may have something to do with it. Sp1 is a so-called transcription factor, which directly binds to the DNA of genes and switches them on. Very little is known about how and where it works. Using novel techniques we can identify all genes within the cell which are bound by Sp1 and we can then test whether they fail to be switched on in its absence. The final outcomes of this work will be (i) a list of genes of which we now know that they are important for forming macrophages, and (ii) a much more detailed understanding of how Sp1 acts in this process. This work is not only of relevance to macrophage biology but also to the understanding of embryogenesis as such.

巨噬细胞是一种白色血细胞，对机体的健康非常重要。这些细胞有能力识别感染性颗粒并发出警报信号，动员身体？的防御合作.但是，在胚胎中，它们具有不同的功能。在这里，他们的功能主要是作为清道夫，并有能力？吃什么？死细胞和细胞碎片，因此在塑造身体轮廓方面起着重要作用。例如，即使在哺乳动物中，手最初也是有蹼的，巨噬细胞会去除手指之间的皮肤。在这里描述的项目中，我们希望解决这种细胞类型如何在胚胎中形成的问题。生物体中所有不同的细胞都起源于同一个卵子;它们之所以不同，是因为它们都表达不同的基因组。因此，我们想知道哪些基因负责产生胚胎巨噬细胞。为了找出哪些基因负责，我们将使用胚胎干细胞（ES）细胞系，该细胞系缺乏一种负责许多基因活性的特定蛋白质（Sp1）。我们发现正常的ES细胞在特殊的培养液中可以转化为胚胎巨噬细胞。然而，在没有Sp1的情况下，这些细胞不会形成。当Sp1在小鼠中被移除时，胚胎无法发育。其原因尚不清楚，但我们的研究表明，巨噬细胞可能与此有关。Sp1是一种所谓的转录因子，它直接与基因的DNA结合并打开它们。关于它如何以及在哪里工作，我们知之甚少。使用新技术，我们可以识别出细胞内所有与Sp1结合的基因，然后我们可以测试它们是否在Sp1缺失的情况下无法启动。这项工作的最终成果将是（i）我们现在知道它们对形成巨噬细胞很重要的基因列表，以及（ii）更详细地了解Sp1在这一过程中的作用。这项工作不仅与巨噬细胞生物学有关，而且与理解胚胎发生有关。