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2013 Fiscal Year Final Research Report

Nicher Regulation for Normal Hemopoietic Stem Cells and Leukemic Stem Cells

Research Project

  • PDF
Project/Area Number 23249053
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKeio University

Principal Investigator

SUDA Toshio  慶應義塾大学, 医学部, 教授 (60118453)

Co-Investigator(Kenkyū-buntansha) TAKUBO Keiyo  慶應義塾大学, 医学部, 専任講師 (50502788)
NAGAMATSU Go  慶應義塾大学, 医学部, 助教 (70453545)
HOSOKAWA Kentaro  慶應義塾大学, 医学部, 特任助教 (90569584)
Project Period (FY) 2011-04-01 – 2014-03-31
Keywords造血幹細胞 / 白血病幹細胞 / ニッチ / 活性酸素 / 低酸素
Research Abstract

Stem cell maintenance in a haltered cell-cycle state (i.e., quiescence) has been proposed as a fundamental property of HSCs. Maintenance of quiescence protects HSCs from functional exhaustion and naturally producing extrinsic cellular insults to enable lifelong hematopoietic cell production. HSC quiescence is regulated through a complex network of cell intrinsic regulations along with extrinsic influences from the microenvironment. Normal HSCs maintain intracellular hypoxia, stabilize the hypoxia-inducible factor-alpha(HIF-1a) protein and generate ATP by anaerobic metabolism. In HIF-1a-deficiency, HSCs became metabolically aerobic, lost cell cycle quiescence, and finally exhausted.

  • Research Products

    (31 results)

All 2014 2013 2012 2011 Other

All Journal Article (19 results) (of which Peer Reviewed: 19 results) Presentation (10 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Haploinsufficiency of SAMD9L, an endosome fusion facilitator, causes myeloid malignancies in mice mimicking human diseases with monosomy 72013

    • Author(s)
      Nagamachi A(他11名)
    • Journal Title

      Cancer Cell

      Volume: 24 Pages: 305-317

    • DOI

      10.1016/j.ccr.2013.08.011

    • Peer Reviewed
  • [Journal Article] Hematopoietic stem cell niche : An interplay among a repertoire of multiple functional niches2013

    • Author(s)
      Nakamura-Ishizu A and Suda T
    • Journal Title

      Biochem BiophysActa

      Volume: 1830 Pages: 2404-2409

    • DOI

      10.1016/j.bbagen.2012.08.023

    • Peer Reviewed
  • [Journal Article] Novel interferon-based pre-transplantation conditioning in the treatment of a congenital metabolic disorder2013

    • Author(s)
      Sato T(他9名)
    • Journal Title

      Blood

      Volume: 121 Pages: 3267-3273

    • DOI

      10.1182/blood-2012-07-443713

    • Peer Reviewed
  • [Journal Article] Regulation of glycolysis by Pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells2013

    • Author(s)
      Takubo K(他12名)
    • Journal Title

      Cell Stem Cell

      Volume: 12 Pages: 49-61

    • DOI

      10.1016/j.stem.2012.10.011.

    • Peer Reviewed
  • [Journal Article] Prostaglandin E(2) regulates murine hematopoietic stem/progenitor cells directly via ER4 receptor and indirectly through mesenchymal progenitor cells2013

    • Author(s)
      Ikushima YM(他7名)
    • Journal Title

      Blood

      Volume: 121 Pages: 1995-2007

    • DOI

      10.1182/blood-2012-06-437889

    • Peer Reviewed
  • [Journal Article] Role of N-cadherin in the regulation of hematopoietic stem cells in the bone marrow niche2012

    • Author(s)
      Arai F(他4名)
    • Journal Title

      Ann NYAcad Sci

      Volume: 1266 Pages: 72-77

    • URL

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566224/

    • Peer Reviewed
  • [Journal Article] A PML-PPAR-δ pathway for fatty acid oxidation regulates hematopoietic stem cell maintenance2012

    • Author(s)
      Ito K(他10名)
    • Journal Title

      Nat Med

      Volume: 18 Pages: 1350-1358

    • DOI

      10.1038/nm.2882

    • Peer Reviewed
  • [Journal Article] Noncanonical Wnt signaling maintains hematopoietic stem cells in the niche2012

    • Author(s)
      Sugimura R(他10名)
    • Journal Title

      Cell

      Volume: 150 Pages: 351-365

    • DOI

      10.1016/j.cell.2012.05.041

    • Peer Reviewed
  • [Journal Article] Pathological neoangiogenesis depends on oxidative stress regulation by ATM2012

    • Author(s)
      Okuno Y(他4名)
    • Journal Title

      Nat Med

      Volume: 18 Pages: 1208-1216

    • DOI

      10.1038/nm.2846

    • Peer Reviewed
  • [Journal Article] Extracellular matrix protein tenascin-C is required in the bone marrow microenvironment primed for hematopoietic regeneration2012

    • Author(s)
      Nakamura-Ishizu A(他8名)
    • Journal Title

      Blood

      Volume: 119 Pages: 5429-5437

    • DOI

      10.1182/blood-2011-11-393645

    • Peer Reviewed
  • [Journal Article] The formation of an angiogenic astrocyte template is regulated by the neuroretina in a HIF-1-dependent manner2012

    • Author(s)
      Nakamura-Ishizu A(他9名)
    • Journal Title

      Dev Biol

      Volume: 363 Pages: 106-114

    • DOI

      10.1016/j.ydbio.2011.12.027

    • Peer Reviewed
  • [Journal Article] Neovascular niche for human myeloma cells in immunodeficient mouse bone2012

    • Author(s)
      Iriuchishima H(他11名)
    • Journal Title

      PloS One

      Volume: 7 Pages: e30557

    • DOI

      10.1371/journal.pone.0030557

    • Peer Reviewed
  • [Journal Article] Hemp, an mbt domain-containing protein, plays essential roles in hematopoietic stem cell function and skeletal formation2011

    • Author(s)
      Honda H(他10名 )
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 108 Pages: 2468-2473

    • DOI

      10.1073/pnas.1003403108

    • Peer Reviewed
  • [Journal Article] Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization2011

    • Author(s)
      Miyamoto K(他19名)
    • Journal Title

      J Exp Med

      Volume: 208 Pages: 2175-2181

    • DOI

      10.1084/jem.20101890

    • Peer Reviewed
  • [Journal Article] p57(Kip2) and p27(Kip1) cooperate to maintain hematopoietic stem cell quiescence through interactions with Hsc702011

    • Author(s)
      Zou P(他9名)
    • Journal Title

      Cell Stem Cell

      Volume: 9 Pages: 247-261

    • DOI

      10.1016/j.stem.2011.07.003

    • Peer Reviewed
  • [Journal Article] Bone marrow-derived cells serve as proangiogenic macrophages but not endothelial cells in wound healing2011

    • Author(s)
      Okuno Y(他4名)
    • Journal Title

      Blood

      Volume: 117 Pages: 5264-5272

    • DOI

      10.1182/blood-2011-01-330720

    • Peer Reviewed
  • [Journal Article] Isolation and function of mouse tissue resident vascular precursors marked by myelin protein zero2011

    • Author(s)
      Kubota Y(他15名)
    • Journal Title

      J Exp Med

      Volume: 208 Pages: 949-960

    • DOI

      10.1084/jem.20102187

    • Peer Reviewed
  • [Journal Article] Telomerase reverse transcriptase protects ATM-deficient hematopoietic stem cells from ROS-induced apoptosis through a telomere-independent mechanism2011

    • Author(s)
      Nitta E(他7名)
    • Journal Title

      Blood

      Volume: 117 Pages: 4169-4180

    • DOI

      10.1182/blood-2010-08-297390

    • Peer Reviewed
  • [Journal Article] Ex vivo maintenance of hematopoietic stem cells by quiescence induction through Fbxw7α overexpression2011

    • Author(s)
      Iriuchishima H(他6名)
    • Journal Title

      Blood

      Volume: 117 Pages: 2373-2377

    • DOI

      10.1182/blood-2010-07-294801

    • Peer Reviewed
  • [Presentation] Hematopoietic stem cells in the hypoxic niche2014

    • Author(s)
      Suda T
    • Organizer
      Keystone Symposia conference 2014 : Sensing and Signaling of Hypoxia: Interfaces with Biology and Medicine
    • Place of Presentation
      Breckenridge, Colorado, USA
    • Year and Date
      20140107-13
  • [Presentation] Hematopoiesis under the stress2013

    • Author(s)
      Suda T
    • Organizer
      Collaborative Meeting of the European and the Spanish Societies for Gene and Cell Therapy Palacio Municipal de Congresos
    • Place of Presentation
      Madrid, Spain
    • Year and Date
      20131025-28
  • [Presentation] A metabolic guide to stem cell homeostasis2013

    • Author(s)
      Suda T
    • Organizer
      Keystone Symposia : Hematopoiesis
    • Place of Presentation
      Steamboat Springs, USA
    • Year and Date
      20130114-19
  • [Presentation] Metabolic regulation of hematopoietic stem cells during stress2012

    • Author(s)
      Suda T
    • Organizer
      Metabolic regulation of hematopoietic stem cells during stress
    • Place of Presentation
      Atlanta, USA
    • Year and Date
      20121208-11
  • [Presentation] Glycolytic metabolism in hematopoietic stem cells.2012

    • Author(s)
      Suda T
    • Organizer
      ICCSR 10th Annual Meeting
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      20120613-16
  • [Presentation] Hematopoietic stem cellmetabolism, Keystone Symposia on Molecular and Cellular Biology2012

    • Author(s)
      Suda T
    • Organizer
      The life of a Stem Cell : From Birth to Death
    • Place of Presentation
      Olympic Valley, USA
    • Year and Date
      20120311-16
  • [Presentation] Hematopoietic stem cells in hypoxic niches2012

    • Author(s)
      Suda T
    • Organizer
      The 2012 Einstein Stem Cell Institute Symposium
    • Place of Presentation
      NY, USA
    • Year and Date
      2012-09-14
  • [Presentation] Regulation of quiescent hematopoietic stem cells2011

    • Author(s)
      Suda T
    • Organizer
      ISEH 40th Annual Scientific Meeting
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      20110825-28
  • [Presentation] Glycolytic metabolism of hematopoieic stem cells2011

    • Author(s)
      Suda T
    • Organizer
      The 2nd ElseKroner-Fresenius Symposium on Molecular Mechanisms of Adult Srtem Cell Aging
    • Place of Presentation
      Gunzgurg, Germany
    • Year and Date
      20110520-22
  • [Presentation] Normal haematopoietic stem cells and the stem cell niche2011

    • Author(s)
      Suda T
    • Organizer
      The 11 th International Symposium on Myelodysplastic Syndromes
    • Place of Presentation
      Edinburgh, UK
    • Year and Date
      20110518-21
  • [Remarks]

    • URL

      http://www.celldiff.med.keio.ac.jp/

  • [Patent(Industrial Property Rights)] 抗がん剤の効果増強剤2012

    • Inventor(s)
      齊藤秀, 小坂威雄, 永松剛, 堀本勝久, 大家基嗣, 須田年生
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      特願 2012-127405
    • Filing Date
      2012-06-04

URL: 

Published: 2015-06-25  

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