Noninvasive Measurement of Hematopoietic Stem Cell Cycling and Turnover by In Vivo Bromodeoxyuridine

The hematopoietic system comprises a concatenated series of stem- and transit-progenitor-cell compartments of progressively restricted potentiality and proliferative capacity (1–5). Analysis of hematopoietic regulation in transplantation models and in marrow regeneration following cytotoxic challenge suggests that normal steady state blood-cell production is ultimately maintained by the progeny of only a few stem-cell clones. The majority of primitive hematopoietic stem cells (PHSC) in the steady state are either highly quiescent or dormant, and are transiently recruited only in times of unusual demand resulting from hematopoietic stress caused by infection, hemorrhage, myelotoxicity, or following transplantation where transiting progenitor-cell compartments need to be replenished. The relative quiescence or dormancy of the stem-cell compartment greatly increases the probability of survival of continuously renewing cell populations by providing a protected stem-cell reserve, thus reducing differentiative pressure and maintaining lifelong genetic stability and integrity of stem cells by facilitating repair (2–6).