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

被引：253

作者：

Matsumoto, Akinobu ^{[1
,2
]}

Takeishi, Shoichiro ^{[1
,2
]}

Kanie, Tomoharu ^{[1
,2
]}

Susaki, Etsuo ^{[1
,2
]}

Onoyama, Ichiro ^{[1
,2
]}

Tateishi, Yuki ^{[1
,2
]}

Nakayama, Keiko ^{[2
,3
]}

Nakayama, Keiichi I. ^{[1
,2
]}

机构：

[1] Kyushu Univ, Med Inst Bioregulat, Dept Mol & Cellular Biol, Higashi Ku, Fukuoka 8128582, Japan

[2] Japan Sci & Technol Agcy JST, CREST, Kawaguchi, Saitama 3320012, Japan

[3] Tohoku Univ, Grad Sch Med, Ctr Translat & Adv Anim Res, Dept Dev Genet,Aoba Ku, Sendai, Miyagi 9808575, Japan

来源：

CELL STEM CELL | 2011年 / 9卷 / 03期

关键词：

TUMOR-SUPPRESSOR; CDK INHIBITOR; MICE LACKING; IN-VIVO; MOUSE DEVELOPMENT; P57(KIP2); P27(KIP1); DIFFERENTIATION; P21(CIP1/WAF1); APOPTOSIS;

D O I：

10.1016/j.stem.2011.06.014

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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 un-characterized. 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.

引用

页码：262 / 271

页数：10

共 30 条

[1] Cdc2-cyclin E complexes regulate the G1/S phase transition [J].