The cell cycle regulator Cdh1 controls the pool sizes of hematopoietic stem cells and mature lineage progenitors by protecting from genotoxic stress

Jo Ishizawa, Shinji Kuninaka, Eiji Sugihara, Hideaki Naoe, Yusuke Kobayashi, Tatsuyuki Chiyoda, Arisa Ueki, Kimi Araki, Ken Ichi Yamamura, Yumi Matsuzaki, Hideaki Nakajima, Yasuo Ikeda, Shinichiro Okamoto, Hideyuki Saya

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Various key cell cycle components, especially G0/G1 regulators, have effects not only on cell proliferation but also on cell differentiation. Cdh1, one of the co-activators that maintain anaphase-promoting complex/cyclosome activity, plays a crucial role in the mitotic phase, but has recently been identified as a G0/G1 regulator, suggesting that the role of Cdh1 in cell differentiation. Here, we generated Cdh1 conditional gene-trap mice to examine Cdh1 functions in adult tissues by overcoming the embryonic lethality of Cdh1 homozygous gene-trap mice. We focused on the hematopoietic system and found that Cdh1-deficient mice exhibited a general decrease in mature lineage progenitor cells and a significant increase in short-term hematopoietic stem cells. This phenomenon became conspicuous by irradiation shortly after Cdh1 downregulation, suggesting that Cdh1 regulates the pool sizes of the hematopoietic stem cells and mature lineage progenitor cells by protecting cells from genotoxic stress. We also found that the irradiation-induced G2/M checkpoint was defective in Cdh1-deficient BM cells, causing the loss of stem/progenitor cells. This is the first report revealing Cdh1 function in adult hematopoiesis and showing a role of Cdh1 in a G2/M checkpoint regulation in vivo.

Original languageEnglish
Pages (from-to)967-974
Number of pages8
JournalCancer Science
Volume102
Issue number5
DOIs
Publication statusPublished - 2011 May

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Cell Lineage
Hematopoietic Stem Cells
DNA Damage
Cell Cycle
Stem Cells
Cell Differentiation
Anaphase-Promoting Complex-Cyclosome
Hematopoietic System
Hematopoiesis
Cellular Structures
Genes
Down-Regulation
Cell Proliferation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The cell cycle regulator Cdh1 controls the pool sizes of hematopoietic stem cells and mature lineage progenitors by protecting from genotoxic stress. / Ishizawa, Jo; Kuninaka, Shinji; Sugihara, Eiji; Naoe, Hideaki; Kobayashi, Yusuke; Chiyoda, Tatsuyuki; Ueki, Arisa; Araki, Kimi; Yamamura, Ken Ichi; Matsuzaki, Yumi; Nakajima, Hideaki; Ikeda, Yasuo; Okamoto, Shinichiro; Saya, Hideyuki.

In: Cancer Science, Vol. 102, No. 5, 05.2011, p. 967-974.

Research output: Contribution to journalArticle

Ishizawa, Jo ; Kuninaka, Shinji ; Sugihara, Eiji ; Naoe, Hideaki ; Kobayashi, Yusuke ; Chiyoda, Tatsuyuki ; Ueki, Arisa ; Araki, Kimi ; Yamamura, Ken Ichi ; Matsuzaki, Yumi ; Nakajima, Hideaki ; Ikeda, Yasuo ; Okamoto, Shinichiro ; Saya, Hideyuki. / The cell cycle regulator Cdh1 controls the pool sizes of hematopoietic stem cells and mature lineage progenitors by protecting from genotoxic stress. In: Cancer Science. 2011 ; Vol. 102, No. 5. pp. 967-974.
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