Slow-cycling/quiescence balance of hematopoietic stem cells is related to physiological gradient of oxygen

ObjectiveRegulation of hematopoiesis depends on cytokines, cellular interactions, transcription, and metabolic factors. Among the latter, O2 has been neglected for a long time. Recently, an increasing number of publications evidenced the regulatory role of physiological low O2 concentrations (0.1−5%; similar to those in bone marrow) on the in vitro behavior of hematopoietic stem cells. This brief review utilizes the article of Eliasson and colleagues in this Journal to summarize the major results and questions about the relationships between O2 and hematopoiesis.Materials and MethodsIn order to be concise and interesting for readers unfamiliar with this field, we selected only the most significant data that either reinforce or contradict the conclusions of Eliasson et al., but we also provide references of reviews with a more detailed bibliography.ResultsA critical analysis of some key publications provides partial answers to three important questions: is the term hypoxia appropriate to describe physiological low O2 concentrations? Is a very low O2 level sufficient to control the quiescence/slow cycling balance of hematopoietic stem cells? Is the O2 concentration able to modify the effect of cytokines on hematopoietic stem cells?ConclusionsWe propose to use in situ normoxia instead of the confusing term hypoxia when working with normal cells at physiological low O2 concentrations. We suggest that a very low O2 concentration is necessary but not sufficient to induce hematopoietic stem cell quiescence. We review some articles showing that O2 variations modify the effect of cytokines.