Detection and functional analysis of cardiac stem cells

• Project/Area Number: 23659096
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Hiroshima University
• Principal Investigator: TAKIHARA Yoshihiro 広島大学, 原爆放射線医科学研究所, 教授 (60226967)
• Co-Investigator(Kenkyū-buntansha): YASUNAGA Shin'ichiro 広島大学, 原爆放射線医科学研究所, 准教授 (50336111) ; SHIRAI Manabu 独立行政法人国立循環器病研究センター, 分子生物部, 室長 (70294121)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 細胞分化 / 組織形成 / 心臓幹細胞 / 再生医学 / ポリコーム複合体 / Geminin

Research Abstract

In this study we further analyzed a molecular role for the Polycomb-rgoup (PcG) complex 1 including Rae28/Phc1 and attempted to identify cardiac stem cells focusing on the expression level of Geminin. PcG complex 1 regulates protein stability through the ubiquitin-proteasome system as well as transcription through the chromatin regulation. We here identified a novel PcG complex with Pcgf5 in the heart and Gemininhighcellular subpopulations in the heart. Since Gemininhighcells reside in the cardiac atrium, in which there previously shown was the presence of cardiac stem cells, these are presumed to be candidates for cardiac stem cells. On the other hand, expression of Geminin is high in S-phase cells, suggesting an intriguing possibility that Gemininhigh cells are proliferating cells in the adult heart.

Research Products

• [Journal Article] Aurora-A controls pre-replicative complex formation and DNA replication by promoting the stabilization of geminin in mitosis (2013)
  • Author(s): Tsunematsu, T., Takihara, Y., Ishimura, N., Pagano, M., Takata, T., Kudo, Y.
  • Journal Title: Nature Commun. Volume: 4 Pages: 1885-1885
  • Peer Reviewed
• [Journal Article] Hoxa9 transduction induces mouse hematopoietic stem and progenitor cell activity through direct down-regulation of Geminin. (2013)
  • Author(s): Ohno, Y., Yasunaga, S., Janmohamed, S., Ohtubo, M., Mihara, K., Iscove, N., Takihara, Y.
  • Journal Title: PLoS ONE Volume: 8(1) Issue: 1 Pages: e53161-e53161
  • DOI: 10.1371/journal.pone.0053161
  • Peer Reviewed
• [Journal Article] Scmh1 has E3 ubiquitin ligase activity for Geminin and histone H2A and regulates Geminin stability directly or indirectly via transcriptional repression of Hoxa9 and Hoxb4 (2013)
  • Author(s): Yasunaga, S., Ohtsubo, M., Ohno, Y., Tanaka-Okamoto, M., Ishizaki, H., Shirai, M., Mihara, K., Brock, W. H., Miyoshi, J., Takihara, Y.
  • Journal Title: Mol. Cell. Biol Volume: 33 Pages: 644-660
  • Peer Reviewed
• [Journal Article] MK3 controls Polycomb-target gene expression via negative feedback on ERK. (2013)
  • Author(s): Prickaerts, P.
  • Journal Title: Epigenetics Chromatin Volume: 5 Issue: 1 Pages: 12-12
  • DOI: 10.1186/1756-8935-5-12
  • Peer Reviewed
• [Journal Article] Scmh1 has E3 ubiquitin ligase activity for Geminin and histone H2A and regulates Geminin stability directly or indirectly via transcription repression of Hoxa9 and Hoxb4 (2013)
  • Author(s): Yasunaga, S., Ohtsubo, M., Ohno, Y., Saeki, K., Kurogi. T., Tanaka-Okamoto, M., Ishizaki, H., Shirai, M., Mihara, K., Brock, H. W., Miyoshi, J. & Takihara Y
  • Journal Title: Mol. Cell. Biol. Volume: 33(4) Issue: 4 Pages: 644-660
  • DOI: 10.1128/mcb.00974-12
  • Peer Reviewed
• [Journal Article] 幹細胞における細胞周期制御特集:がん幹細胞研究の新たな展開 (2012)
  • Author(s): 瀧原義宏、安永晋一郎、大野芳典、大坪素秋
  • Journal Title: 血液フロンティア(医薬ジャーナル社) Volume: 22 Pages: 33-43
• [Journal Article] Role for Geminin in sustaining the activity of hematopoietic stem cells. (2011)
  • Author(s): Takihara, Y.
  • Journal Title: Cell Cycle Volume: 10 Pages: 561-562
  • Peer Reviewed
• [Journal Article] 造血幹細胞の守護神Geminin (2011)
  • Author(s): 瀧原義宏
  • Journal Title: 原医研ニュース Volume: 2 Pages: 6-7
• [Presentation] Novel molecular regulatory network governing Geminin maintains hematopoietic homeostasis. (2012)
  • Author(s): Takihara, Y., Yasunaga, S., Ohno, Y., Saeki, K., Nakashima, Y., Ohtsubo, M.
  • Organizer: 41st annual scientific meeting of the international society for hematology and stem cells
  • Place of Presentation: Amsterdam, Netherlands
• [Presentation] Scmh1, a member of Polycomb-complex 1, maintains hematopoietic homeostasis through the regulation of Geminin protein stability (2012)
  • Author(s): Takihara, Y., Ohno, Y.,Yasunaga, S., Saeki, K., Kurogi, T., Nakashima, Y., Ohtsubo, M.
  • Organizer: International symposium: Genetic and Epigenetic Control of Cell Fate
  • Place of Presentation: Kyoto
• [Presentation] Functional analysis of Pcgf5 (Polycomb Ring Finger 5) gene during Cardiogenesis. (2012)
  • Author(s): Shirai, M., Takihara, Y., Morisaki, T
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] Scmh1 is required for maintaining hematopoietic homeostasis through the molecular network governing Geminin expression. (2012)
  • Author(s): Ohno, Y., Yasunaga, S., Saeki, K., Ohtsubo, M., Kurogi, T., Nakashima, Y., Takihara, Y.
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] Molecular role for Geminin in E2F-mediated transcriptional regulation (2012)
  • Author(s): Saeki, K., Ohno, Y., Yasunaga, S., Ohtsubo, M., Kurogi, T., Nakashima, Y., Takihara, Y.
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] 心臓発生における、ポリコーム遺伝子群の発現及び機能解析 (2012)
  • Author(s): 白井 学、瀧原義宏、森崎隆幸
  • Organizer: 日本心臓血管発生研究会
  • Place of Presentation: 熱海
• [Presentation] ポリコーム複合体1と Hoxb4による Geminin 制御と造血幹細胞活性 (2012)
  • Author(s): 瀧原義宏
  • Organizer: 特定領域研究「細胞増殖制御」終了シンポジウム
  • Place of Presentation: 東京
• [Presentation] ポリコーム遺伝子群の心臓形態形成に対する発現・機能解析 (2012)
  • Author(s): 白井 学
  • Organizer: 心臓血管発生研究会
  • Place of Presentation: 郡山
• [Presentation] ポリコーム遺伝子群の心臓形態形成に対する発現・機能解析 (2011)
  • Author(s): 白井 学、瀧原義宏、森崎隆幸
  • Organizer: 心臓血管発生研究会
  • Place of Presentation: 郡山
• [Presentation] Distribution of Polycomb-group proteins in the developing heart (2011)
  • Author(s): Shirai, M., Takihara, Y., Morisaki, T
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Distribution of Polycomb-group proteins in the developing heart
  • Author(s): Shirai, M.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Remarks]
  • URL: http://home.hiroshima-u.ac.jp/dscb/
• [Remarks]
  • URL: http://home.hiroshima-u.ac.jp/dscb/