P57 Is required for quiescence and maintenance of adult hematopoietic stem cells

Akinobu Matsumoto, Shoichiro Takeishi, Tomoharu Kanie, Etsuo Susaki, Ichiro Onoyama, Yuki Tateishi, Keiko Nakayama, Keiichi Nakayama

研究成果: ジャーナルへの寄稿記事

162 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)262-271
ページ数10
ジャーナルCell stem cell
9
発行部数3
DOI
出版物ステータス出版済み - 9 2 2011

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Adult Stem Cells
Hematopoietic Stem Cells
Maintenance
Cyclin-Dependent Kinase Inhibitor p57
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinase Inhibitor p27
Gastrin-Secreting Cells

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Molecular Medicine
  • Genetics

これを引用

P57 Is required for quiescence and maintenance of adult hematopoietic stem cells. / Matsumoto, Akinobu; Takeishi, Shoichiro; Kanie, Tomoharu; Susaki, Etsuo; Onoyama, Ichiro; Tateishi, Yuki; Nakayama, Keiko; Nakayama, Keiichi.

:: Cell stem cell, 巻 9, 番号 3, 02.09.2011, p. 262-271.

研究成果: ジャーナルへの寄稿記事

Matsumoto, Akinobu ; Takeishi, Shoichiro ; Kanie, Tomoharu ; Susaki, Etsuo ; Onoyama, Ichiro ; Tateishi, Yuki ; Nakayama, Keiko ; Nakayama, Keiichi. / P57 Is required for quiescence and maintenance of adult hematopoietic stem cells. :: Cell stem cell. 2011 ; 巻 9, 番号 3. pp. 262-271.
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AU - Matsumoto, Akinobu

AU - Takeishi, Shoichiro

AU - Kanie, Tomoharu

AU - Susaki, Etsuo

AU - Onoyama, Ichiro

AU - Tateishi, Yuki

AU - Nakayama, Keiko

AU - Nakayama, Keiichi

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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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