Spatio-temporal dynamics of hematopoietic stem cell (HSC) interaction with the HSC niche during migration and engraftment

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Hematopoietic stem cells (HSC) are essential for the continuous supply of healthy blood cells throughout an organism’s life span. For many hematological diseases, stem cell transplantation (SCT) represents the only available curative option. Despite decades of clinical application, the molecular mechanisms that govern successful migration and integration of transplanted HSC from the bloodstream to their target tissues (the stem cell niche) remain widely elusive. Migration of HSCs occurs not only during SCT, but also under steady state conditions. The cells of the HSC niche are thought to be crucial for successful engraftment, yet the lack of appropriate models has so far precluded a comprehensive definition of this HSC-recruiting niche cell population.The aim of this project is to explore the interplay between HSCs and their niche during engraftment. The findings of this study may uncover actionable targets for the modulation of the engraftment process. To this end, we plan to: 1) localize target organs and niches of HSCs and progenitor cells in the early stages (hours to days) of SCT, 2) define niche cells that are crucially involved in HSC engraftment, and 3) identify relevant factors and signals produced by the HSC-recruiting niche cell population. In preparation for this project, the applicant has prepared novel reporter mouse models in the host laboratory that allow for the tracking of HSCs in vivo and permit fluorescence-based visualization of HSC-niche cell interactions. A better understanding of the mechanisms orchestrating HSC engraftment will potentially open new avenues for improving hematologic reconstitution after SCT.