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

造血干细胞和前体细胞（HSPC）需要额外的骨髓细胞（所谓的小生境细胞）的输入和支持，以维持血细胞的稳态。然而，大多数支持不同小生境细胞调节作用的数据要么基于组织解剖学跨区域研究单位FOR 2033：Nichem研究，要么间接来自不同骨髓隔室中HSPC功能或HSPC含量变化的观察结果，这些变化由不同小生境组分的调节诱导。新的成像模型，应用2-光子活体显微镜（2 P-IVM），现在已经建立了我们和其他人允许直接可视化的动态之间的相互作用骨髓和龛细胞在体内。在本项目中，我们将使用2 P-IVM（1）分析移植或内源性HSPC与体内不同小生境细胞之间的动态相互作用，以及（2）量化克隆HSPC扩增期间这些细胞群体之间的相互作用。(3)此外，我们将解决，无论是血统分化的限制和不同的BM壁龛内划分。作为模型谱系，我们将使用巨核细胞及其前体细胞。(4)最后，HSPC-生态位串扰中涉及的分子特征将特别关注CXCL 12/CXCR 4信号通路的作用。

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.