Vinculin is indispensable for hematopoietic stem cell repopulation

• Project/Area Number: 21790920
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: Jichi Medical University
• Principal Investigator: OHMORI Tsukasa Jichi Medical University, 医学部, 講師 (70382843)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 造血幹細胞移植学 / インテグリン / 造血幹細胞 / Talin / 細胞骨格

Research Abstract

Vinculin is a highly conserved actin-binding protein that is localized in integrin-mediated focal adhesion complexes. This study showed that the ability of c-Kit+Sca1+Lin- (KSL) hematopoietic stem cells (HSCs) to support reconstitution of hematopoiesis after competitive transplantation was severely impaired by lentiviral transduction with short hairpin RNA sequences for vinculin, albeit adhesion to the extracellular matrix and homing to bone marrow were not inhibited. Our results suggest that vinculin is an indispensable factor determining HSC repopulation capacity, independent of integrin functions.

Research Products

• [Journal Article] Vinculin is indispensable for repopulation by hematopoietic stem cells, independent of integrin function. (2010)
  • Author(s): Ohmori T., Kashiwakura Y., Ishiwata A., Madoiwa S., Mimuro J., Furukawa Y., Sakata Y.
  • Journal Title: J Biol Chem. 285(41) Pages: 31763-31773
• [Journal Article] Vinculin activates inside-out signaling of integrin αIIbβ3 in Chinese hamster ovary cells. (2010)
  • Author(s): Ohmori, T., Kashiwakura Y., Ishiwata A., Madoiwa S., Mimuro J., Honda S., Miyata T., Sakata Y.
  • Journal Title: Biophy Biochem Res Commun 400(3) Pages: 323-328
• [Journal Article] VINCULIN IS INDISPENSABLE FOR REPOPULATION BY HEMATOPOIETIC STEM CELLS, INDEPENDENT OF INTEGRIN FUNCTION (2010)
  • Author(s): Ohmori T, Kashiwakura Y, Ishiwata A, Madoiwa S, Mimuro J, Furukawa Y, Sakata Y.
  • Journal Title: Journal of Biological Chemistry Volume: 285(41) Pages: 31763-73
  • Peer Reviewed
• [Journal Article] VINCULIN ACTIVATES INSIDE-OUT SIGNALING OF INTEGRIN ALPHAIIBBETA3 IN CHINESE HAMSTER OVARY CELLS (2010)
  • Author(s): Ohmori T, Kashiwakura Y, Ishiwata A, Madoiwa S, Mimuro J, Honda S, Miyata T, Sakata Y.
  • Journal Title: Biochem Biophys Res Commun Volume: 400(3) Pages: 323-8
  • Peer Reviewed
• [Journal Article] Mutant Macaque Factor IX T262A : A Tool for Hemophilia B Gene Therapy Studies in Macaques. (2010)
  • Author(s): Ishiwata, A.
  • Journal Title: Thrombosis Reseach (in press)
  • Peer Reviewed
• [Journal Article] Impact of acute cellular rejection on coagulation and fibrinolysis biomarkers within the immediate post-operative period in pediatric liver transplantation. (2010)
  • Author(s): Mimuro, J.
  • Journal Title: Pediatr Transplant. (In press)
  • Peer Reviewed
• [Journal Article] Liver-restricted expression of the canine factor VIII gene facilitates prevention of inhibitor formation in factor VIII-deficient mice. (2009)
  • Author(s): Ishiwata, A.
  • Journal Title: J Gene Med. 11(11) Pages: 1020-1029
  • Peer Reviewed
• [Journal Article] Induction of factor VIII-specific unresponsiveness by intrathymic factor VIII injection in murine hemophilia A. (2009)
  • Author(s): Madoiwa, S.
  • Journal Title: J Thromb Haemost. 7(5) Pages: 811-824
  • Peer Reviewed
• [Presentation] VINCULIN IS INDISPENSABLE FOR REPOPULATION BY HEMATOPOIETIC STEM CELLS (2010)
  • Author(s): 大森司
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2010-09-24
• [Presentation] Platelet-directed gene therapy for hemophilia by lentiviral vector. (2010)
  • Author(s): Ohmori T., Sakata Y.
  • Organizer: The 6^<th> Congress of Asia Pacific Society on Thrombosis and Haemostasis(シンポジウム)
  • Place of Presentation: Nusa Dua Bali
• [Presentation] Vinculin is indispensable for repopulation by hematopoietic stem cells. (2010)
  • Author(s): 大森司, 柏倉裕志, 石渡彰, 窓岩清治, 三室淳, 古川雄佑, 坂田洋一
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Platelet-directed gene modification by lentiviral vector. (2009)
  • Author(s): 大森司, 窓岩清治, 三室淳, 坂田洋一
  • Organizer: 第71回日本血液学会学術集会(シンポジウム)
  • Place of Presentation: 京都
• [Presentation] Platelet-directed gene modiffication by lentiviral vector (2009)
  • Author(s): Tsukasa Ohmori
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都
• [Presentation] Robust and sustained factor IX expression following IV injection of AAV8-based vectors in magaques. (2009)
  • Author(s): 水上浩明
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都
• [Presentation] Promoter selection for muscle-directed self-complementary AAV toward hemophilia B gene therapy. (2009)
  • Author(s): 久米晃浩
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都
• [Presentation] 高純度AAV8、AAV9ベクター精製法の確立 (2009)
  • Author(s): 石渡彰
  • Organizer: 第32回日本血栓止血学会学術集会
  • Place of Presentation: 北九州
• [Presentation] GPIba遺伝子近傍のクロマチンインスレーター配列の同定 (2009)
  • Author(s): Thasinas Dissayabutra
  • Organizer: 第32回日本血栓止血学会学術集会
  • Place of Presentation: 北九州
• [Book] Hematopoietic stem cell repopulation after transplantation.(Stem Cells and Cancer Stem Cells : Therapeutic Applications in Disease and Injury, Volume 2)
  • Author(s): Ohmori T., Sakata Y.
  • Publisher: Springer(in press).
• [Book] STEM CELLS AND CANCER STEM CELLS
  • Author(s): Ohmori T, Sakata Y.
  • Publisher: Springer(印刷中)
• [Remarks] ホームページ等