Schema of in vivo expansion. (A) A HSC replicates and produces 2 daughter cells, both of which retain the HSC phenotype. The paired daughter HSCs in the stem cell pool contribute to hematopoiesis; even so, the self-renewal activity of the parent HSC may be equally distributed to both daughters or may be skewed to either daughter cell. (B) As a result of heterogeneous HSC replication, one of the daughter HSCs loses the stem cell potential and therefore exits from the stem cell pool, but still remains in the progenitor pool. (C) Both paired daughter cells have lost their HSC potential, leading to exhaustion from the stem cell pool. 34 indicates CD34⁺ stem/progenitor cells; M, CD33⁺ myeloid lineage cells; B, CD19⁺ B-lymphoid lineage cells; T, CD3⁺ (spleen) or CD4/CD8 double-positive (thymus) T-lymphoid lineage cells.