Maintenance of hematopoietic stem cell dormancy: yet another role for the macrophage

Hematopoietic stem cells (HSC) possess several unique features that ensure a life-long supply of all bone marrow derived blood cell lineages (1). In adulthood, they are mainly localized to the bone marrow and depend on a supportive niche for maintaining their long-term (LT) repopulating ability while simultaneously having a capacity for multi-potent differentiation. The HSC niche has been suggested to be composed of vascular endothelial cells, perivascular mesenchymal stromal cells (2-4), osteoblasts (5) as well as mature hematopoietic cells like megakaryocytes and macrophages (6-9). Furthermore, HSC maintain a low cell cycle activity to prevent exhaustion of their replicative capacity (10). In addition, recent findings suggest that HSC can be subdivided into LT or short-term (ST) HSC of which the latter have a greater propensity for lineage-specific differentiation (11). Mouse LT-HSCs are enriched in a cell population immunophenotypically characterized as Lin⁻ (lineage negative), c-Kit⁺, Sca1⁺, CD150⁺, CD34⁻, Flk2/Flt3⁻ and CD48⁻ cells. A recent study adds expression of Hoxb5 to these markers for providing additional definition of the LT-HSC population (12).