Analysis of Hematopoietic stem cell regulation through Polycomb-group complex 1

• Project/Area Number: 21602004
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Stem cell biology and medical science
• Research Institution: Beppu University (2011); Hiroshima University (2009-2010)
• Principal Investigator: OHTSUBO Motoaki 別府大学, 食物栄養科学部, 教授 (10211799)
• Co-Investigator(Kenkyū-buntansha): TAKIHARA Yoshihiro 広島大学, 原爆放射線医科学研究所, 教授 (60226967) ; YASUNAGA Shin ichiro 広島大学, 原爆放射線医科学研究所, 准教授 (50336111) ; OHNO Yoshinori 広島大学, 原爆放射線医科学研究所, 助教 (10548986)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 再生医学 / 発生・分化 / 造血幹細胞 / ポリコーム複合体 / Geminin / DNA複製制御 / DMA複製制御

Research Abstract

We revealed that Polycomb-group(PcG) complex 1 regulates the protein's stability of Geminin either by directly acting as the E3 ubiquitin ligase or indirectly through transcriptional regulation of Hoxa9 and Hoxb4.Our observations will contribute to the development of a method to enhance hematopoietic stem cell activity by manipulating the E3 ubiquitin ligase activity of PcG complex 1 through the modification of Scmh1.

Research Products

• [Journal Article] Overexpression of BMI-1 correlates with drug resistance in B-cell lymphoma cells through the stabilization of surviving expression (2012)
  • Author(s): Bhattacharyya, J., Mihara, K., Ohtsubo, M., Yasunaga, S., Takei, Y., Yanagihara, K., Sakai, A., Hishi, M., Takihara, Y., Kimura, A.
  • Journal Title: Cancer Science Volume: 103(1) Pages: 34-41
  • Peer Reviewed
• [Journal Article] Decreased expression in nuclear factor-kB essential modulator due to a novel splice-site mutation causes X-linked ectodermal dysplasia with immunodeficiency (2011)
  • Author(s): Karakawa, S., Okada, S., Tsumura, M., Mizoguchi, Y., Ohno, N., Yasunaga, S., Ohtsubo, M., Kawai, T., Nishikomori, R., Sakaguchi, T., Takihara, Y., Kobayashi, M.
  • Journal Title: Journal of Clinical Immunology Volume: 31(5) Pages: 762-772
  • Peer Reviewed
• [Journal Article] Molecular pathogenesis of a novel mutation, G108D, in short-chain acyl-CoA dehydrogenase identified in subjects with short-chain acyl-CoA dehydrogenase deficiency (2010)
  • Author(s): Shirao, K., Okada, S., Tajima, G., Tsumura, M., Hara, K., Yasunaga, S., Ohtsubo, M., Hata, I., Sakura, N., Shigematsu, Y., Takihara, Y., Kobayashi, M.
  • Journal Title: Human Genetics Volume: 127(6) Pages: 619-628
  • Peer Reviewed
• [Journal Article] Hoxb4 transduction down-regulates Geminin protein, providing hematopoietic stem and progenitor cells with proliferation potential (2010)
  • Author(s): Ohno, Y., Yasunaga, S., Ohtsubo, M., Mori, S., Tsumura, M., Okada, S., Ohta, T., Ohtani, K., Kobayashi, M., Takihara, Y.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 107 Pages: 21529-21534
  • NAID: 40019027599
  • Peer Reviewed
• [Journal Article] Hoxb4 transduction down-regulates Geminin protein, providing hematopoietic stem and progenitor cells with proliferation potential. (2010)
  • Author(s): Ohno, Y., Yasunaga, S., Ohtsubo, M., Mori, S., Tsumura, M., Okada, S., Ohta, T., Ohtani, K., Kobayashi, M., Takihara, Y.
  • Journal Title: Proc.Natl.Acad.Sci.USA Volume: 107 Pages: 21529-21534
  • NAID: 40019027599
  • Peer Reviewed
• [Journal Article] Molecular pathogenesis of a novel mutation, G108D, in short-chain acyl-CoA dehydrogenase identified in subjects with short-chain acyl-CoA dehydrogenase deficiency. (2010)
  • Author(s): Shirao, K., Okada, S., Tajima, G., Tsumura, M., Hara, K., Yasunaga, S., Ohtsubo, M., Hata, I., Sakura, N., Shigematsu, Y., Takihara, Y., Kobayashi, M.
  • Journal Title: Hum.Genet. Volume: 127(6) Pages: 619-628
  • Peer Reviewed
• [Presentation] Role for an Scmh1-mediated molecular network governing Geminin expression in hematopoiesis (2012)
  • Author(s): Ohtsubo, M., Yasunaga, Y., Ohno, Y., Kawashima, A., Tetsuguchi, H., Saeki, K., Nakashima, Y., Takihara, Y.
  • Organizer: International Symposium 50^<th> Anniversary of RIRBM, Hiroshima University
  • Place of Presentation: 広島国際会議場
  • Year and Date: 2012-02-21
• [Presentation] Hole for an Scmh1-mediated molecular network governing Geminin expression in hematopoiesis (2012)
  • Author(s): Ohtsubo, M., Yasunaga, Y., Ohno, Y., Kawashima, A., Tetsuguchi, H., Saeki, K, Nakashima, Y., Takihara, Y.
  • Organizer: International Symposium 50^<th> Anniversary of RIRBM, Hiroshima University
  • Place of Presentation: 広島国際会議場
  • Year and Date: 2012-02-21
• [Presentation] A new strategy for maintaining HSC activity through the modulation of Geminin expression (2011)
  • Author(s): Yasunaga, Y., Ohno, Y., Ohtsubo, M., Furutani, T., Kawashima, A., Tetsuguchi, H., Saeki, K., Nakashima, Y., Takihara, Y.
  • Organizer: 日本血液学会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-15
• [Presentation] Study of a 5-FU-induced stabilization signal for Scmh1, a component of Polycomb-group complex 1 E3 ligase (2009)
  • Author(s): Ohtsubo, M., Yasunaga, S., Ohno, Y., Tsumura, M., Kageyama, Y., Mori, S., Takihara, Y.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-10
• [Presentation] Study of a 5-FU-induced stabilization signal for Scmhl, a component of Polycomb-group complex 1 E3 ligase (2009)
  • Author(s): 大坪素秋
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-10
• [Presentation] HSCの活性維持に必須なポリコーム複合体1の構成因子Scmh1の機能ドメインの解析 (2009)
  • Author(s): 大坪素秋
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2009-10-23
• [Presentation] HSCの活性維持に必須なポリコーム複合体1の構成因子 Scmhl の機能ドメインの解析 (2009)
  • Author(s): 大坪素秋
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2009-10-23
• [Presentation] Role of Scmh1 in the regulation of Polycomb-group complex 1, which acts as the E3 ubiquitin ligase for histone H2A and Geminin (2009)
  • Author(s): Ohtsubo, M., Yasunaga, S., Tsumura, M., Ohno, Y., Kageyama, Y., Kimura, S., Tokimoto, R., Takihara, Y.
  • Organizer: The 7th Stem Cell Research Symposium
  • Place of Presentation: Tokyo
  • Year and Date: 2009-05-16
• [Book] 血液フロンティア・がん幹細胞研究の新たな展開・幹細胞における細胞周期制御 (2012)
  • Author(s): 瀧原義宏,安永晋一郎,大野芳典,大坪素秋
  • Publisher: 医薬ジャーナル社
• [Book] 血液フロンティア・がん幹細胞研究の新たな展開・幹細胞における細胞周期制御 (2012)
  • Author(s): 瀧原義宏、安永晋一郎、大野芳典、大坪素秋
  • Total Pages: 11
  • Publisher: 医薬ジャーナル社
• [Remarks]
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