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This lecture covers the relevance of hematopoietic stem cells (HSCs) in therapy and basic science, including their normal function, hierarchy, sources, and transplantation procedures. It delves into the clinical applications of HSC transplantation, focusing on autologous vs. allogeneic grafts, donor compatibility, key events in blood reconstitution, and the success rates and complications of HSC transplantation. The lecture also explores functional stem cell assays, the identification of HSCs in bone marrow, and the assessment of HSC function through in vivo and in vitro assays.