Analysis of hematopoietic stem cell regulation through Geminin ubiquitination

• Project/Area Number: 20610003
• 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: Hiroshima University
• Principal Investigator: YASUNAGA Shin'ichiro Hiroshima University, 原爆放射線医科学研究所, 助教 (50336111)
• Co-Investigator(Kenkyū-buntansha): OHTSUBO Motoaki 広島大学, 原爆放射線医科学研究所, 助教 (10211799) ; TAKIHARA Yoshihiro 広島大学, 原爆放射線医科学研究所, 教授 (60226967)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 再生医学 / ユビキチン化 / Geminin / ポリコーム複合体 / HOXB4 / 造血幹細胞 / E3ユビキチンリガーゼ / 自己複製

Research Abstract

We revealed that each of Polycomb complex 1 (Ring1B-Bmi1-Rae28-Scmh1 wild type) and RDCOXB4 complex (Roc1-Ddb1-Cul4a-HOXB4 wild type) acts as an E3 ubiquitin ligase for Geminin to regulate expression level of the protein, which sustains hematopoietic stem cell activity. Next, we succeeded in generating Geminin-EYFP knock-in mice to trace the expression level of Geminin in vivo hematopoiesis.

Research Products

• [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. 107(50) Pages: 21529-21534
  • Peer Reviewed
• [Journal Article] Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anto-CD38 chimeric receptor in conjunction with rituximab on B-cell non-Hodgkin lymphoma. (2010)
  • Author(s): Mihara, K., Yanagihara, K., Takigahira, M., Imai, C., Bhattacharyya, J., Kubo, T., Takei, Y., Yasunaga, S., Takihara, Y..Kimura, A.
  • Journal Title: Br.J.Haematol. 151(1) Pages: 37-46
  • Peer Reviewed
• [Journal Article] Molecular pathogenesis of 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. 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., et.al.
  • Journal Title: Proc.Natl.Acad.Sci. Volume: 107 Pages: 21529-21534
  • Peer Reviewed
• [Journal Article] Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anto-CD38 chimeric receptor in conjunction with rituximab on B-cell non-Hodgkin lymphoma. (2010)
  • Author(s): Mihara, K., et.al.
  • Journal Title: Br.J.Haematol. Volume: 151 Pages: 37-46
  • Peer Reviewed
• [Journal Article] Molecular pathogenesis of novel mutation, G108D, in short-chain acyl-CoA dehydrogenase identified in subjects with short-chain acyl-CoA dehydrogenase deficiency. (2010)
  • Author(s): Shirao, K., et.al.
  • Journal Title: Hum.Genet. Volume: 127 Pages: 619-628
  • Peer Reviewed
• [Journal Article] Cardiac infiltration in early-onset sarcoidosis associated with a novel heterozygous mutation, G481D, in CARD15. (2009)
  • Author(s): Okada, S., Konishi, N., Tsumura, M., Shirao, K., Yasunaga, S., Sakai, H., Nishikomori, R., Takihara, Y., Kobayashi, M.
  • Journal Title: Rheumatology (Oxford) 48(6) Pages: 706-707
  • Peer Reviewed
• [Journal Article] BMI-1 expression is enhanced through transcriptional and posttranscriptional regulation during progression of chronic myeloid leukemia. (2009)
  • Author(s): Bhattacharyya, J., Mihara, K., Yasunaga, S., Tanaka, H., Hoshi, M., Takihara, Y., Kimura, A.
  • Journal Title: Ann. Hematol. 88(4) Pages: 333-340
  • Peer Reviewed
• [Journal Article] BMI-1 expression is enhanced through transcriptional and posttranscri-ptional regulation during progression of chronic mveloid leukemia (2009)
  • Author(s): Bhattacharyya, J., et al.
  • Journal Title: Ann.Hematol. 88 Pages: 333-340
  • Peer Reviewed
• [Journal Article] Cardiac infiltration in early-onset sarcoidosis associated with a novel heterozygous mutation, G481D, in CARD15 (2009)
  • Author(s): Okada, S., et al.
  • Journal Title: Rheumatology (Oxford) 48 Pages: 706-707
  • Peer Reviewed
• [Journal Article] Polycomb-group complex 1 acts as an E3 ubiquitin ligase for Geminin to sustain hematopoietic stem cell activity. (2008)
  • Author(s): Ohtsubo, M., Yasunaga, S., Ohno, Y., Tsumura, M., Okada, S., Ishikawa, N., Shirao, K., Kikuchi, A., Nishitani, H., Kobayashi, M., Takihara Y
  • Journal Title: Proc.Natl.Acad.Sci. 105(30) Pages: 10396-10401
  • Peer Reviewed
• [Journal Article] Polycomb-group complex 1 acts as an E3 ubiquitin ligase for Geminin to sustain hematopoietic stem cell activity. (2008)
  • Author(s): Ohtsubo M., Yasunaga Y. & Takihara Y., et al.
  • Journal Title: Proc. Natl. Acad. Sci. 105 Pages: 10396-10401
  • Peer Reviewed
• [Presentation] Scmhl deficiency up-regulates transcription of Hox genes to maintain the expression level of Geminin, that may play a crucial role for sustaining hematopoiesis. (2011)
  • Author(s): Yasunaga S., Ohtsubo M., Ohno Y., Mori S., Furutani T., Kawashima A., Tetsuguchi H., Nakashima Y., Takihara Y.
  • Organizer: The First RIRBM International SymposiumBMB : Genome damage and non-cancerous diseases
  • Place of Presentation: Hiroshima, Japan.
• [Presentation] Scmhl, a member of Polycomb complex 1, regulates hematopoiesis either through Geminin Ubiquitination or through repression of Hox genes. (2010)
  • Author(s): Yasunaga S., Ohtsubo M., Ohno Y., Mori S., Furutani T., Kawashima A., Tetsuguchi H., Nakashima Y., Takihara Y.
  • Organizer: BMB (Biochemistry and Molecular Biology) 2010
  • Place of Presentation: Kobe, Japan.
• [Presentation] A role for Geminin in sustaining activity of Haemopoietic stem and progenitor cells. (2010)
  • Author(s): Yasunaga S., Ohno Y., Ohtsubo M., Tsumura M., Mori S., Nakashima Y., Kobayashi M., Takihara Y.
  • Organizer: The 72^<nd> Annual Meeting of the Japanese Society of Hematology
  • Place of Presentation: Yokohama, Japan.
• [Presentation] Role for Geminin in hematopoietic stem cell regulation. (2010)
  • Author(s): Yasunaga S., Ohno Y., Ohtsubo M, Tsumura, M., Kageyama Y., Mori S., Nakashima Y., Takihara Y.
  • Organizer: The 8^<th> Stem Cell Research Symposium
  • Place of Presentation: Awaji, Japan.
• [Presentation] A role for Geminin in sustaining activity of haemopoietic stem and progenitor cells. (2010)
  • Author(s): Yasunaga, S., et.al.
  • Organizer: The 72^<nd> Annual Meeting of the Japanese Society of Hematology
  • Place of Presentation: 横浜
• [Presentation] Scmh1, a member of Polycomb complex 1, regulates hematopoiesis either through Geminin Ubiquitination or through repression of Hox genes (2010)
  • Author(s): Yasunaga, S., et.al.
  • Organizer: BMB(Biochemistry and Molecular Biology)2010
  • Place of Presentation: 神戸
• [Presentation] Molecular role of Scmhl, a member of Polycomb complex 1. Which plays a crucial role for governing the hematopoietic stem cell activity. (2009)
  • Author(s): Yasunaga S., Ohtsubo M., Ohno Y., Tsumura, M., Kageyama Y., Mori S., Nakashima Y., Takihara Y.
  • Organizer: The 32^<nd> Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: Yokohama, Japan.
• [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、安永晋一郎、津村弥来、大野芳典、影山由佳、森彩華、時元利恵、小林正夫、瀧原義宏
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 京都
• [Presentation] Molecular role of Scmhl, a member of Polycomb complex 1. Which plays a crucial role for governing the hematopoietic stem cell activity. (2009)
  • Author(s): 安永晋一郎, 大野芳典, 大坪素秋, 津村弥来, 影山由佳, 時元利恵, 瀧原義宏
  • Organizer: The 7^<th> Stem Cell Research Symposium
  • Place of Presentation: Tokyo, Japan.
• [Presentation] Molecular role of Scmhl, a member of Polycomb complex 1, which plays acrucial role for governing the hematopoietic stem cell activity (2009)
  • Author(s): 安永晋一郎, et al.
  • Organizer: The 32^<nd> Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: 横浜
• [Presentation] Scmh1よる造血幹細胞制御機構の解析 (2009)
  • Author(s): 安永晋一郎, 他
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 京都
• [Presentation] Gemininによる造血幹細胞制御の分子基盤 (2008)
  • Author(s): 安永晋一郎、大坪素秋、大野芳典、影山由佳、津村弥来、岡田賢、時元利恵、小林正夫、瀧原義宏
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会・合同大会
  • Place of Presentation: 神戸
• [Presentation] 造血幹細胞制御におけるGemininの役割 (2008)
  • Author(s): 安永晋一郎、大坪素秋、大野芳典、影山由佳、津村弥来、岡田賢、石川暢恒、白尾謙一郎、時元利恵、小林正夫、瀧原義宏
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
• [Remarks] ホームページ等
  • URL: http://home.hiroshima-u.ac.jp/dscb/index.html
• [Remarks]
  • URL: http://home.hiroshima-u.ac.jp/dscb