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

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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.