The impact of transcriptomic imprinting on the functional specialization of monocytes during health and disease

转录组印记对健康和疾病期间单核细胞功能特化的影响

• 批准号: 282795005
• 负责人: Professor Dr. Andreas Schlitzer
• 金额: --
• 依托单位: Life and Medical Sciences Institute (LIMES)
• 依托单位国家: 德国
• 项目类别: Independent Junior Research Groups
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/282795005?language=en
• 关键词: impact; transcriptomic; imprinting; functional; specialization

The mononuclear phagocyte lineage consists of dendritic cells (DCs), monocytes and macrophages and is crucial for initiation, maintenance and control of immune responses. Additionally, crucial roles during the induction and maintenance of tolerance have been assigned to members of the this lineage. Recent advances using cutting edge technologies, such as single cell mRNA sequencing, cytometry by time of flight (CyToF), flow cytometry and in vivo transfers enabled us to get an in depth understanding of the origin and functional specialization of DC subsets and the development thereof. Monocytes however, albeit one of the largest and functional most diverse cell compartments in mouse and man remain poorly characterized. Phenotypic and functional specialization can be observed at every stage of the monocyte life cycle and it is not well understood how such a heterogeneous cell subset is transcriptomically, developmentally, and functionally regulated. Therefore the proposals central question will be the transcriptional and developmental regulation of the functional specialization of mouse (Ly6c+) and human (CD14+) monocyte subsets during health and disease. In detail the proposal will investigate the functional specialization of human and mouse monocytes during steady state, across lymphoid and non-lymphoid tissues, to determine the impact of Nature vs. Nurture during the functional specialization of Ly6c+ monocytes. Moreover the regulation and transcriptional basis of monocyte dependent trained immunity will be investigated during various inflammatory models such as vaccination induced inflammation and intestinal inflammation. This proposal will utilize cutting edge technologies such as single cell mRNA sequencing, CyToF and multicolour flow cytometry paired with functional characterization to delineate for the first time the functional specialization of human and mouse monocyte subsets during health and disease.

单核吞噬细胞谱系由树突状细胞 (DC)、单核细胞和巨噬细胞组成，对于免疫反应的启动、维持和控制至关重要。此外，该谱系的成员在诱导和维持耐受性过程中发挥着关键作用。使用单细胞 mRNA 测序、飞行时间细胞计数 (CyToF)、流式细胞术和体内转移等尖端技术的最新进展使我们能够深入了解 DC 亚群的起源和功能特化及其发展。然而，尽管单核细胞是小鼠和人类中最大且功能最多样化的细胞区室之一，但其特征仍然很少。在单核细胞生命周期的每个阶段都可以观察到表型和功能特化，但目前尚不清楚这种异质细胞亚群是如何在转录组、发育和功能上受到调节的。因此，建议的核心问题将是健康和疾病期间小鼠（Ly6c+）和人类（CD14+）单核细胞亚群功能特化的转录和发育调节。具体而言，该提案将研究人类和小鼠单核细胞在稳态期间跨越淋巴和非淋巴组织的功能特化，以确定先天与后天在 Ly6c+ 单核细胞功能特化过程中的影响。此外，还将在各种炎症模型（例如疫苗接种诱导的炎症和肠道炎症）中研究单核细胞依赖性训练免疫的调节和转录基础。该提案将利用单细胞 mRNA 测序、CyToF 和多色流式细胞术等尖端技术与功能表征相结合，首次描述人类和小鼠单核细胞亚群在健康和疾病期间的功能特化。