Aging of hematopoietic stem cells - unrevealed role of Neogenin-1 /Netrin-1 axis.
Hematopoietic stem cells (HSCs) sustain production of all blood cells through the lifetime. However, HSCs gradually lose their regenerative potential during aging. The project will check whether bone marrow (BM) niche drives age-related disturbances among HSCs. Proposed experiments will verify if the changes in the niche acquired during aging contribute to decline in function of HSC in elderly individuals. We will verify the possible mechanism of HSC-niche interactions during aging. Our preliminary data suggests that Neogenin-1 (Neo-1)/Netrin-1 (Ntn-1) axis may be implicated in niche-driven aging of HSC. To verify our hypothesis we proposed approach based on new transgenic mouse models. Finally, we check whether Neo-1 defines the aging fraction of human HSCs and whether Ntn-1 is conserved among human BM niche. The project will contribute to understanding how bone-marrow niche regulates aging of HSCs and how this knowledge can be translated to clinical application.
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