CDK6 levels regulate quiescence exit in human hematopoietic stem cells
Life-long production of blood cells is guaranteed by rare haematopoietic stem cells (HSC), which divide very infrequently and spend most of the time in an inactive, quiescent state. The HSC pool is not homogeneous but rather comprises distinct HSC subsets that differ in their functional properties. This heterogeneity is crucial to ensure that the shifting needs of blood demand can be rapidly met in normal and injury situations. However the molecular mechanisms underlying the distinct behaviour of HSC subsets are unknown. Laurenti et al. show that, within the human HSC compartment, there are 2 HSC subsets that differ in the duration of a division once they are stimulated to divide. The authors have identified CDK6 as the key protein responsible for the different division timings observed within the human HSC pool. They also demonstrated experimentally and by computational modelling that differential control of the duration of quiescence exit helps maintaining blood production in the long-term. If the expression of CDK6 increases in the most primitive HSC subset, which normally does not express this protein, these cells gain a competitive advantage over other HSC and expand. Perturbation of the duration of quiescence exit could thus play an important role in the very first steps of leukaemia.
Laurenti, Elisa et al. CDK6 Levels Regulate Quiescence Exit in Human Hematopoietic Stem Cells. Cell Stem Cell. PMID: 25704240