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Role of Geminin in cell fate determination of hematopoietic stem cells (HSCs)

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Abstract

Geminin exerts two distinct molecular roles. Geminin negatively regulates DNA replication licensing through the direct interaction with Cdt1 to prevent re-replication in proliferating cells. Geminin also regulates chromatin remodeling through the direct interaction with Brahma/Brg1 to maintain undifferentiated states of stem cells. We previously uncovered that Polycomb-group complex 1 and Hoxb4/Hoxa9, well-known intrinsic factors that are essential for maintaining the hematopoietic stem cell (HSC) activity, alternatively act as ubiquitin–proteasome systems for Geminin protein to reduce the protein expression level, and sustain the HSC activity. Thus, Geminin is presumed to play an important role in determining cell fate, i.e., turning on and off cellular quiescence and proliferation/differentiation, in HSCs. We recently generated recombinant cell-penetrating Geminin (CP-Geminin), enabling rapid incorporation and withdraw of Geminin protein in cells. CP-Geminin may be useful in regulating the cell cycle and chromatin configuration. In this article, we summarize current information on the molecular functions of Geminin and the regulatory system for Geminin protein expression, and argue for the molecular role of Geminin in cell fate determination of HSCs, and future perspective of a new technology for manipulating the activities of HSCs and cancer stem cells (CSCs).

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Acknowledgments

This work was supported by Grants-in-Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science and Technology of Japan, the Naito foundation, the Life Science Foundation of Japan, the Takeda Science Foundation and the Radiation Effects Association. We would like to thank Ms. Hiromi Yamada for her secretarial work.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan

    Shin’ichiro Yasunaga, Naoto Shirasu & Bo Zhang

  2. Department of Stem Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan

    Shin’ichiro Yasunaga, Yoshinori Ohno, Kyoko Suzuki-Takedachi, Motoaki Ohtsubo & Yoshihiro Takihara

  3. Department of Food and Fermentation Science, Faculty of Food Science and Nutrition, Beppu University, 82 Kitaishigaki, Beppu, Oita, 874-0915, Japan

    Motoaki Ohtsubo

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  1. Shin’ichiro Yasunaga
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  2. Yoshinori Ohno
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Correspondence to Shin’ichiro Yasunaga.

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Yasunaga, S., Ohno, Y., Shirasu, N. et al. Role of Geminin in cell fate determination of hematopoietic stem cells (HSCs). Int J Hematol 104, 324–329 (2016). https://doi.org/10.1007/s12185-016-2060-9

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  • DOI: https://doi.org/10.1007/s12185-016-2060-9

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