Allogenic hematopoietic stem cell transplant (allo-HSCT) is a curative therapy for patients suffering from bone marrow failure, severe immune deficiency, inborn errors of metabolism, and leukemia. Albeit potentially life-saving, the success of HSCT is hampered by non-engraftment of the transplanted HSCs and by treatment-related side-effects, such as immune reactions, life-threatening infections and hemorrhagic complications. Administration of sufficient HSCs is crucial to prevent many of these immediate risks. Moreover, polyclonal hematopoietic reconstitution (i.e. by multiple HSCs) may be favorable on the long-term, as age-related decline in the number of HSC clones predisposes to leukemia, cardiovascular disease and death. The ultimate goal of my project is to gain fundamental insight into the clonal dynamics by which HSCs regenerate blood after transplantation in human recipients, and to characterize the impact of transplantation on the genomic and functional integrity of these cells.