Output without input: the lifelong productivity of hematopoietic stem cells

The hematopoietic stem cell (HSC) compartment must be maintained life-long, while being replenishable only from within. HSC proliferation can compensate for cell loss by differentiation, by cell death, or by mobilization from the bone marrow niches, but the relative use of proliferation to compensate for these distinct depletion sources is unclear. Classifications of HSC states (e.g., as active, dormant, quiescent or parsimonious) have mostly been based on HSC proliferation rather than on actual differentiation arising from HSC. New in vivo fate mapping experiments have shed light on HSC output. The kinetics of label emergence from HSC to progenitor stages uncovered steady, infrequent and low output from large numbers of HSC during normal adult hematopoiesis. Here, we discuss the relative contribution of proliferation to differentiation and self-renewal in hematopoietic stem and progenitor compartments, and propose that kinetic data on HSC output also yield insights into the structure of the hematopoietic hierarchy.