Molecular mechanism of the establishment and maintenance of the nteraction between hematopoietic stem cells and osteoblastic niche

2008 Fiscal Year Final Research Report

• Project/Area Number: 18689024
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: Keio University
• Principal Investigator: ARAI Fumio Keio University, 医学部, 講師 (90365403)
• Project Period (FY): 2006 – 2008
• Keywords: 造血幹細胞 / 幹細胞ニッチ / 骨芽細胞

Research Abstract

造血幹細胞の未分化性維持には骨芽細胞性ニッチとの相互作用が重要であり、その制御にMpl/Thrombopoietin、N-cadherinが重要な機能を果たしていることを同定した。また、骨芽細胞性ニッチは分化段階の異なる複数の細胞により構成されることを見いだした。さらに、ニッチ分子の機能阻害により、幹細胞がニッチから離れ、活性化されることがわかった。これは、ニッチ分子の機能修飾により、造血幹細胞の動態を制御できることを示しており、今後、低侵襲条件での幹細胞移植をはじめとした再生医療に応用できると考えられた。

Research Products

• [Journal Article] Reconstitution activity of hypoxic cultured human cord blood CD34-positive cells in NOG mice. (2009)
  • Author(s): Shima H, Takubo K, Iwasaki H, Yoshihara H, Gomei Y, Hosokawa K, Arai F, Takahashi T, Suda T.
  • Journal Title: Biochem Biophys Res Commun 378 Pages: 467-472
  • Peer Reviewed
• [Journal Article] Angiopoietins contribute to lung development by regulating pulmonary vascular network formation. (2009)
  • Author(s): Hato T, Kimura Y, Morisada T, Koh GY, Miyata K, Tabata M, Kadomatsu T, Endo M, Urano T, Arai F, et al.
  • Journal Title: Biochem Biophys Res Commun 381 Pages: 218-223
  • Peer Reviewed
• [Journal Article] Wnt signaling in the niche. (2008)
  • Author(s): Suda T, Arai F.
  • Journal Title: Cell 132 Pages: 729-730
• [Journal Article] dentification of stem cells during prepubertal spermatogenesis via monitoring of nucleostemin promoter activity. (2008)
  • Author(s): Ohmura M, Naka K, Hoshii T, Muraguchi T, Shugo H, Tamase A, Uema N, Ooshio T, Arai F, Takubo K, Nagamatsu G, Hamaguchi I, Takagi M, Ishihara M, Sakurada K, Miyaji H, Suda T, Hirao A.
  • Journal Title: Stem Cells. 26 Pages: 3237-3246
  • Peer Reviewed
• [Journal Article] Fbxw7 acts as a critical failsafe against premature loss of hematopoietic stem cells and development of T-ALL. (2008)
  • Author(s): Matsuoka S, Oike Y, Onoyama I, Iwama A, Arai F, Takubo K, Mashimo Y, Oguro H, Nitta E, Ito K, Miyamoto K, Yoshiwara H, Hosokawa K, Nagamatsu G, Nakamura Y, Gomei Y, Iwasaki H, Shima H, Hayashi Y, Matsuzaki Y, Nakayama K, Ikeda Y, Hata A, Chiba S, Nakayama KI, Suda T.
  • Journal Title: Genes Dev 22 Pages: 986-991
  • Peer Reviewed
• [Journal Article] Stem Cell defects in ATM-deficient undifferentiated spermatogonia through DNA damage-induced cell cycle arrest. (2008)
  • Author(s): Takubo K, Ohmura M, Azuma M, Nagamatsu G, Yamada W, Arai F, Hirao A, Suda T.
  • Journal Title: Cell Stem Cell. 2 Pages: 170-182
  • Peer Reviewed
• [Journal Article] Thrombopoietin/Mpl signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche. (2007)
  • Author(s): Yoshihara H, Arai F, Hosokawa K, Hagiwara T, Takubo K, Nakamura Y, Gomei Y, Iwasaki H, Matsuoka S, Miyamoto K, Miyazaki H, Takahashi T, Suda T.
  • Journal Title: Cell Stem Cell. 363 Pages: 685-697
  • Peer Reviewed
• [Journal Article] Function of oxidative stress in the regulation of hematopoietic stem cell-niche interaction. (2007)
  • Author(s): Hosokawa K, Arai F, Yoshihara H, Nakamura Y, Gomei Y, Iwasaki H, Miyamoto K, Shima H, Ito K, Suda T.
  • Journal Title: Biochem Biophys Res Commun. 363 Pages: 578-583
  • Peer Reviewed
• [Journal Article] Foxo3a is essential for maintenance of hematopoietic stem cell pool. (2007)
  • Author(s): Miyamoto K, Araki K, Naka K, Arai F, Takubo K, Yamazaki S, Matsuoka S, Miyamoto T, Ito K, Ohmura M, Chen C, Hosokawa K, Nakauchi H, Nakayama K, Nakayama K-I, Harada M, Motoyama N, Suda T, Hirao A.
  • Journal Title: Cell Stem Cell. 1 Pages: 101-112
  • Peer Reviewed
• [Journal Article] Regulation of reactive oxygen species by Atm is essential for proper response to DNA double strand breaks in lymphocytes. (2007)
  • Author(s): Ito K, Takubo K, Arai F, Satoh H, Matsuoka S, Ohmura M, Naka K, Azuma M, Miyamoto K, Hosokawa K, Ikeda Y, Mak TW, Suda T, Hirao A.
  • Journal Title: J. Immunol. 178 Pages: 103-110
  • Peer Reviewed
• [Journal Article] Homing, proliferation and survival sites of human leukemia cells in vivo in immunodeficient mice. (2007)
  • Author(s): Ninomiya M, Abe A, Katsumi A, Xu J, Ito M, Arai F, Suda T, Ito M, Kiyoi H, Kinoshita T, Naoe T.
  • Journal Title: Leukemia. 21(1) Pages: 136-142
  • Peer Reviewed
• [Journal Article] Premeiotic germ cell defect in seminiferous tubules of Atm-null testis. (2006)
  • Author(s): Takubo K, Hirao A, Ohmura M, Azuma M, Arai F, Nagamatsu G, Suda T.
  • Journal Title: Biochem Biophys Res Commun. 351 Pages: 993-998
  • Peer Reviewed
• [Journal Article] Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. (2006)
  • Author(s): Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K, Ohmura M, Naka K, Hosokawa K, Ikeda Y and Suda T.
  • Journal Title: Nat Med, 12 Pages: 446-451
  • Peer Reviewed
• [Journal Article] Regulation of hematopoietic stem cell and its interaction with stem cell niche. (2006)
  • Author(s): Arai F.
  • Journal Title: J Oral Biosci 48 Pages: 22-29
  • Peer Reviewed
• [Journal Article] Cadherin-based adhesion is a otential target for niche nipulation to protect matopoietic stem cells in adult bone marrow
  • Author(s): Hsokawa K, Arai F, Yoshihara H, wasaki H, Hembree M, Yin T, akamura N, Gomei Y, Takubo K, hiama H, Matsuoka S, Li L, Suda T.
  • Journal Title: Cell Stem Cell (in press)
  • Peer Reviewed
• [Journal Article] IRF-2 protects quiescent HSCs from type-I interferon-dependent exhaustion.
  • Author(s): Sato T, Onai N, Yoshihara H, Arai F ,Suda T, Ohteki T.
  • Journal Title: Nat Med (in press)
  • Peer Reviewed
• [Presentation] Hematopoietic stem cell niche (2009)
  • Author(s): Arai F.
  • Organizer: The 5th General Assembly with Asian Symposium-2009
  • Place of Presentation: Kobe, Japan.
  • Year and Date: 20090213-14
• [Presentation] Niche regulation of hematopoietic stem cells in the endosteum. (2008)
  • Author(s): Arai F.
  • Organizer: International Conference and Workshop. Hematopoietic Stem Cells VII.
  • Place of Presentation: Meersburg, Germany
  • Year and Date: 20080918-20
• [Presentation] Regulation of the hematopoietic stem cell and its interaction with the osteoblastic niche. (2007)
  • Author(s): Arai F.
  • Organizer: Gordon Research Conference, Bone & Teeth
  • Place of Presentation: University of New England, Biddeford, ME, USA
  • Year and Date: 20070715-20
• [Presentation] Interaction of N-cadherin with b-catenin is involved in then maintenance of hematopoietic stem cell quiescence in the osteoblastic niche. (2007)
  • Author(s): Arai F, Hosokawa K, Yoshihara H, Takubo K, Matsuoka S, Miyamoto K, Nakamura Y, Gomei Y, Suda T.
  • Organizer: 5th International Society for Stem Cell Research Annual Meeting
  • Place of Presentation: Cairns, Australia.
  • Year and Date: 20070617-20
• [Presentation] Maintenance of stem cells in the niche. International Conference and Workshop. (2006)
  • Author(s): Arai F.
  • Organizer: Hematopoietic Stem Cells VI.
  • Place of Presentation: Tubingen, Germany.
  • Year and Date: 20060914-16
• [Presentation] Regulation of hematopoietic stem cells in the osteoblastic niche. (2006)
  • Author(s): Arai F.
  • Organizer: 1st International Conference on Osteoimmunology : Interaction of the Immune and Skeletal Systems.
  • Place of Presentation: Crete, Greece.
  • Year and Date: 20060528-0602
• [Presentation] Regulation of hematopoietic stem cell and its interaction with stem cell niche. (2006)
  • Author(s): Arai F.
  • Organizer: Hiroshima conference on education and science in dentistry, 2006.
  • Place of Presentation: Hiroshima, Japan
  • Year and Date: 20060108-09
• [Presentation] Regulation of hematopoietic stem cells by the niche. (2006)
  • Author(s): Arai F.
  • Organizer: Stem Cell Biology and Regenerativec Medicine-from Bench to Bedside.
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2006-01-14
• [Book] Regulation of hematopoietic stem cells in the osteoblastic niche. Osteoimmunology : Interactions of the Immune and Skeletal System (Choi Y, edited) (2007)
  • Author(s): Arai F, Suda T.
  • Total Pages: 61-67
  • Publisher: Adv Exp Med Biol.
• [Book] Maintenance of quiescent hematopoietic stem cells in the osteoblastic niche. Hematopoietic Stem Cells VI. (2007)
  • Author(s): Arai F, Suda T.
  • Total Pages: 41-53
  • Publisher: Ann N Y Acad Sci
• [Book] Landes Bioscience/Eurekah.com (2006)
  • Author(s): Arai F, Suda T.
  • Total Pages: 92-107
  • Publisher: Endothelial and hematopoietic cells in the intraembryonic compartment. In Hematopoietic Stem Cell Development. (edited by Godin I and Cumano A)