Abstract
Hematopoietic stem cell (HSC) hierarchy based on transplantation assays defines long-term (LT), intermediate term and short-term stem cells. Recent studies showed that the LT-HSC pool is functionally heterogeneous and that HSCs vary in their differentiation potential and length of reconstitution but display unpredictable differences on the magnitude of repopulation. Transplanting single LT-HSCs into into non-conditioned recipient mice allowed for the identification of two distinct functional stem cell stages that robustly repopulate primary recipient mice but that differ in the magnitude of engraftment. Stage I LT-HSCs are quiescent cells that express genes mapping to cellular adhesion pathways and that have excessive clonal expansion capacity after transplantation whereas stage II LT-HSCs express genes mapping to metabolic pathways and display limited proliferative capacity. Transplantation of prospectively separated stem cell subtypes revealed that stage I cells precede stage II LT-HSCs during differentiation, suggesting that initiation of differentiation is marked by the transit from stage I to stage II LT-HSCs.
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