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Development of cmyb-independent macrophages from the primitive hematopoiesis

原始造血过程中不依赖 cmyb 的巨噬细胞的发育

基本信息

批准号：
252963971
负责人：
Professorin Dr. Katrin Kierdorf
金额：
--
依托单位：
Immunology Program
依托单位国家：
德国
项目类别：
Research Fellowships
财政年份：
2013
资助国家：
德国
起止时间：
2012-12-31 至 2017-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/252963971?language=en
关键词：
Development cmyb independent macrophages primitive

项目摘要

In order to understand the role of tissue macrophages in homeostasis and disease, we have to analyze and identify the embryonic origin of these important immune cells. Recently, it was reported that two subpopulations of tissue macrophages, originating from primitive and definitive hematopoiesis, exist next to each other in adult organs. Whereas essential factors for the differentiation of myeloid cells from the definitive hematopoiesis are well defined, there is only scarce knowledge about factors guiding primitive myelopoiesis in the yolk sac.In the following research project I want to address basic and essential questions regarding the primitive hematopoiesis and the origin of cmyb-independent macrophages.I want to define exogenous and endogenous factors essential for the primitive hematopoiesis in the yolk sac. Key factors of the stromal compartment required for the induction of macrophages will be identified and characterized first. This will provide evidence whether the key factors for macrophage development in the yolk sac are identical or different to those in the fetal liver or in the adult bone marrow. Furthermore, a detailed characterization of the different myeloid progenitors of the cmyb independent tissue macrophages will define which specific surface molecules are expressed on these cells. With these data available a lineage specific marker might be identified to identify, trace and target cmyb-independent macrophages.In the next step I want to follow the migration routes and characterize the distribution of tissue macrophages from the yolk sac, clarifying the order of colonization during embryonic development. Finally I want to analyze the presumably different functions of cmyb-dependent and cmyb-independent tissue macrophages in homeostasis and inflammation in an animal model of metabolic syndrome. With these results available we will gain a deeper insight into the origin and function of cmyb-independent tissue macrophages, leading to a better understanding on the role of these unique cells in physiological and pathophysiological settings.

为了了解组织巨噬细胞在体内平衡和疾病中的作用，我们必须分析和鉴定这些重要免疫细胞的胚胎起源。最近，据报道，两个亚群的组织巨噬细胞，起源于原始和永久造血，存在于成人器官中彼此相邻。尽管从永久性造血分化出髓样细胞的基本因素已经明确，在下面的研究项目中，我想解决有关原始造血和cmyb起源的基本和本质问题，独立的巨噬细胞。我想定义卵黄囊中原始造血所必需的外源性和内源性因素。首先将识别和表征诱导巨噬细胞所需的基质隔室的关键因素。这将为卵黄囊中巨噬细胞发育的关键因素与胎儿肝脏或成人骨髓中的巨噬细胞发育的关键因素是否相同或不同提供证据。此外，cmyb非依赖性组织巨噬细胞的不同髓系祖细胞的详细表征将确定哪些特异性表面分子在这些细胞上表达。有了这些数据，一个谱系特异性标记物可能被确定，以识别，跟踪和靶向cmyb非依赖性macrophages.In下一步，我想遵循的迁移路线和组织中的分布特征的巨噬细胞从卵黄囊，澄清在胚胎发育过程中的殖民秩序。最后，我想分析在代谢综合征动物模型中，cmyb依赖性和cmyb非依赖性组织巨噬细胞在稳态和炎症中可能的不同功能。有了这些结果，我们将获得更深入的了解cmyb非依赖性组织巨噬细胞的起源和功能，从而更好地了解这些独特的细胞在生理和病理生理环境中的作用。