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Identification of factors regulating fate and function of microglia and macrophages in the CNS.

中枢神经系统中小胶质细胞和巨噬细胞命运和功能调节因素的鉴定。

基本信息

批准号：
279642606
负责人：
Professor Dr. Marco Prinz
金额：
--
依托单位：
Institut für Neuropathologie
依托单位国家：
德国
项目类别：
Reinhart Koselleck Projects
财政年份：
2015
资助国家：
德国
起止时间：
2014-12-31 至 2020-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/279642606?language=en
关键词：
Identification factors regulating fate function

项目摘要

The brain hosts a heterogeneous population of myeloid cells, including parenchymal microglia (MG), perivascular & meningeal macrophages and choroid plexus macrophages (M). In addition to functions during development myeloid cells are crucially involved in virtually all CNS diseases and myeloid dysfunction is thought to be causal for a group of diseases, called microgliopathies. Novel genetic and imaging methodologies will be employed by us to elucidate myeloid cell fate, diversity and function on single cell level. My proposal is pillared by three main approaches: First (Aim 1), we will challenge the classical few on the origin and fate of M. These cells are thought to be short lived and to derive, in contrast to yolk sac-derived MG , from circulating cells. Our prelimary data suggest a complete opposing view and suppose a different lineage. Second (Aim 2), kinetics and dynamics of MG & M networks during health and disease will be examined in vivo by using a new multicolour fluorescence fate mapping system that will provide new insights into cell homeostasis and renewal. Third (Aim 3), a distinct genetic signature in MG & M is thought to be the basis of their diverse biological functions. By applying massively parallel single cell RNAseq we will uncover their heterogeneity on single cell level in steady state. We expected that our results will fundamentally change our traditional view on brain myeloid cells.

脑中存在异质的髓样细胞群，包括实质小胶质细胞（MG）、血管周围和脑膜巨噬细胞和脉络丛巨噬细胞（M）。除了发育过程中的功能外，骨髓细胞还与几乎所有中枢神经系统疾病密切相关，骨髓功能障碍被认为是一组称为小胶质细胞病的疾病的病因。我们将采用新的遗传学和成像方法来阐明单个细胞水平上的骨髓细胞命运、多样性和功能。我的建议是由三个主要途径支柱：第一（目标1），我们将挑战经典的起源和命运的M少数。这些细胞被认为是短寿命的，并且与卵黄囊来源的MG相反，它们来自循环细胞。我们的初步数据提出了一个完全相反的观点，并假设了一个不同的血统。第二（目标2），MG & M网络在健康和疾病期间的动力学和动力学将通过使用新的多色荧光命运映射系统在体内进行检查，该系统将为细胞稳态和更新提供新的见解。第三（目标3），MG & M中独特的基因特征被认为是其多种生物学功能的基础。通过应用大规模并行单细胞RNAseq，我们将在稳态下揭示它们在单细胞水平上的异质性。我们期望我们的结果将从根本上改变我们对脑髓样细胞的传统看法。