In vivo analysis of hematopoietic stem/progenitor cell interaction with the niche

造血干/祖细胞与微环境相互作用的体内分析

• 批准号: 245330109
• 负责人: Professor Dr. Steffen Massberg
• 金额: --
• 依托单位: Medizinische Klinik und Poliklinik I (Kardiologie) - Campus Großhadern
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/245330109?language=en
• 关键词: vivo; analysis; hematopoietic; stem; progenitor

Hematopoietic stem and precursor cells (HSPC) need the input and support from additional bone marrow cells, so-called niche cells, in order to maintain blood cell homeostasis. However, most of the data supporting the regulatory role of distinct niche cells is either based on histo-anatomical Transregional Research Unit FOR 2033: NicHem studies or indirectly arises from observations of changes in HSPC function or HSPC content in different bone marrow compartments, induced by modulation of distinct niche components. New imaging models applying 2-photon-intravital microscopy (2P-IVM), have now been established by us and others allowing direct visualisation of dynamic interactions between bone marrow and niche cells in vivo. In this project, we will use 2P-IVM (1) to analyse the dynamic interactions between transplanted or endogenous HSPC and distinct niche cells in vivo and (2) to quantify the interaction between those cell populations during clonal HSPC expansion. (3) Further, we will address, whether lineage differentiation is restricted to and compartmentalized within distinct BM niches. As a model lineage, we will use megakaryocytes and their precursors. (4) Finally, the molecular signatures involved in HSPC-niche cross-talk will be addressed with a specific focus on the role of the CXCL12/CXCR4 signalling pathway.

造血干细胞和前体细胞（HSPC）需要额外的骨髓细胞（所谓的生态位细胞）的输入和支持，以维持血细胞的稳态。然而，大多数支持不同生态位细胞调节作用的数据要么是基于组织解剖跨区域研究单位FOR 2033: NicHem研究，要么间接来自不同骨髓腔室中HSPC功能或HSPC含量变化的观察，这些变化是由不同生态位成分的调节引起的。我们和其他人已经建立了新的成像模型，应用2光子活体显微镜（2P-IVM），可以直接观察骨髓和体内小生境细胞之间的动态相互作用。在这个项目中，我们将使用2P-IVM(1)分析移植或内源性HSPC与体内不同生态位细胞之间的动态相互作用；(2)量化克隆HSPC扩增过程中这些细胞群体之间的相互作用。(3)此外，我们将讨论谱系分化是否局限于不同的BM生态位，并在不同的BM生态位中划分。作为一个模型谱系，我们将使用巨核细胞及其前体。(4)最后，将重点讨论hspc -生态位串扰的分子特征，并特别关注CXCL12/CXCR4信号通路的作用。