<i>Polycomb</i> Group Gene <i>rae28</i> Is Required for Sustaining Activity of Hematopoietic Stem Cells

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  • Hideaki Ohta
    1Department of Developmental Biology and Medicine, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan
  • Akihisa Sawada
    1Department of Developmental Biology and Medicine, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan
  • Ji Yoo Kim
    1Department of Developmental Biology and Medicine, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan
  • Sadao Tokimasa
    1Department of Developmental Biology and Medicine, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan
  • Seiji Nishiguchi
    2Department of Medical Genetics, Research Institute for Microbial Diseases, Osaka University
  • R. Keith Humphries
    4The Terry Fox Laboratory, British Columbia Cancer Agency and the Department of Medicine, University of British Columbia, Vancouver, BC, Canada V5Z 1L3
  • Junichi Hara
    3Department of Developmental Medicine, Osaka University Graduate School of Medicine, Suita 565-0871, Japan
  • Yoshihiro Takihara
    1Department of Developmental Biology and Medicine, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan

抄録

<jats:p>The rae28 gene (rae28), also designated as mph1, is a mammalian ortholog of the Drosophila polyhomeotic gene, a member of Polycomb group genes (PcG). rae28 constitutes PcG complex 1 for maintaining transcriptional states which have been once initiated, presumably through modulation of the chromatin structure. Hematopoietic activity was impaired in the fetal liver of rae28-deficient animals (rae28−/−), as demonstrated by progressive reduction of hematopoietic progenitors of multilineages and poor expansion of colony forming units in spleen (CFU-S12) during embryonic development. An in vitro long-term culture-initiating cell assay suggested a reduction in hematopoietic stem cells (HSCs), which was confirmed in vivo by reconstitution experiments in lethally irradiated congenic recipient mice. The competitive repopulating units (CRUs) reflect HSCs supporting multilineage blood-cell production. CRUs were generated, whereas the number of CRUs was reduced by a factor of 20 in the rae28−/− fetal liver. We also performed serial transplantation experiments to semiquantitatively measure self-renewal activity of CRUs in vivo. Self-renewal activity of CRUs was 15-fold decreased in rae28−/−. Thus the compromised HSCs were presumed to reduce hematopoietic activity in the rae28−/− fetal liver. This is the first report to suggest that rae28 has a crucial role in sustaining the activity of HSCs to maintain hematopoiesis.</jats:p>

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