Hematopoietic stem cells (HSCs) drive reconstitution of the bone marrow and peripheral blood after hematopoietic stem cell transplant (HSCT). At baseline (pre-HSCT), the bone marrow contains the recipient’s cells (colored red). Following transplant, donor HSCs (colored differently to reflect single clones) are introduced into the bone marrow space. Initially, some HSCs undergo “symmetric differentiation” (colored black, yellow, orange, gray, brown, and green) into progenitor “non-HSCs” that undergo further division and contribute to early neutrophil recovery; however, those HSCs are not retained in the long-lived HSC pool. In contrast, those HSCs that undergo predominantly “symmetric HSC expansion” (colored blue, pink, and purple) repopulate the HSC niche by expanding to form clonal pools. At later time points, some of the HSCs from these clonal pools will differentiate and repopulate the peripheral blood long term.