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In vivo imaging of haematopoietic stem cells in their natural niches to uncover cellular and molecular dynamics regulating self-renewal

Final Report Summary - HSCNICHEIVM (In vivo imaging of haematopoietic stem cells in their natural niches to uncover cellular and molecular dynamics regulating self-renewal)

Through this project we have greatly increased our understanding of the interactions between blood stem cells and the bone marrow microenvironment. We have uncovered how multiple types of stress (from infection to leukaemia growth) change the composition of the bone marrow microenvironment, and this as a consequence affects blood stem cells numbers and function. For example, we have uncovered how infection reduce stem cell signatures and stem cell function, and this can be modulated by targeting their environment. Leukaemia too alters the bone marrow microenvironment, eliminating healthy cells from the tissue partly in an indiscriminatory manner, partly through direct ablation of stem cell niches in late stages of disease. In this case too, targeting the bone marrow microenvironment can rescue stem cells numbers. These findings are very important because they elucidate the consequences of multiple stresses on blood stem cells, and provide clues for the development of improved therapeutic approaches that will prevent stem cell damage. Ultimately, these will enable us to prevent haematological disease and enjoy healthy ageing.