TY - JOUR
T1 - P57 Is required for quiescence and maintenance of adult hematopoietic stem cells
AU - Matsumoto, Akinobu
AU - Takeishi, Shoichiro
AU - Kanie, Tomoharu
AU - Susaki, Etsuo
AU - Onoyama, Ichiro
AU - Tateishi, Yuki
AU - Nakayama, Keiko
AU - Nakayama, Keiichi I.
PY - 2011/9/2
Y1 - 2011/9/2
N2 - Quiescence 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 G 0 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.
AB - Quiescence 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 G 0 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.
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U2 - 10.1016/j.stem.2011.06.014
DO - 10.1016/j.stem.2011.06.014
M3 - Article
C2 - 21885021
AN - SCOPUS:80052289298
SN - 1934-5909
VL - 9
SP - 262
EP - 271
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 3
ER -