title: p57 is required for quiescence and maintenance of adult hematopoietic stem cells.
abstract: 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.
authors: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan.
authors: Akinobu
authors: A
authors: Matsumoto
authors: Shoichiro
authors: S
authors: Takeishi
authors: Tomoharu
authors: T
authors: Kanie
authors: Etsuo
authors: E
authors: Susaki
authors: Ichiro
authors: I
authors: Onoyama
authors: Yuki
authors: Y
authors: Tateishi
authors: Keiko
authors: K
authors: Nakayama
authors: Keiichi I
authors: KI
authors: Nakayama
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D048708:Cell Growth Processes / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics; D003114:Colony-Forming Units Assay; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics / Q000378:metabolism*; D055879:Gene Knock-In Techniques; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; C493965:Cdkn1c protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050761:Cyclin-Dependent Kinase Inhibitor p57; D018809:Proliferating Cell Nuclear Antigen; C413374:p27 antigen