p57 Is Required for Quiescence and Maintenance of Adult Hematopoietic Stem Cells

SummaryQuiescence is required for the maintenance of hematopoietic stem cells (HSCs). Members of the Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors (p21, p27, p57) have been implicated in HSC quiescence, but loss of p21 or p27 in mice affects HSC quiescence or functionality only under conditions of stress. Although p57 is the most abundant family member in quiescent HSCs, its role has remained uncharacterized. Here we show a severe defect in the self-renewal capacity of p57-deficient HSCs and a reduction of the proportion of the cells in G0 phase. Additional ablation of p21 in a p57-null background resulted in a further decrease in the colony-forming activity of HSCs. Moreover, the HSC abnormalities of p57-deficient mice were corrected by knocking in the p27 gene at the p57 locus. Our results therefore suggest that, among Cip/Kip family CDK inhibitors, p57 plays a predominant role in the quiescence and maintenance of adult HSCs.

► p57 is the most abundant CDK inhibitor in quiescent hematopoietic stem cells (HSCs)
► p57 deficiency in hematopoietic cells resulted in a decrease in the HSC population
► p57-deficient HSCs lost the ability to reconstitute the hematopoietic system
► Maintenance of quiescence was defective in p57-deficient HSCs