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DNA damage response in human hematopoietic stem cell

Research Project

Project/Area Number 22790299
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionTokai University

Principal Investigator

YAHATA Takashi  東海大学, 医学部, 講師 (10398753)

Co-Investigator(Renkei-kenkyūsha) ANDO Kiyoshi  東海大学, 医学部, 教授 (70176014)
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords再生医学 / 造血幹細胞 / 移植 / 酸化ストレス / DNA障害 / 再生医療 / ヒト化モデル動物 / DNA損傷 / 自己複製 / 幹細胞移植 / ヒト化モデルマウス
Research Abstract

Stem cells of highly regenerative organs including blood are susceptible to endogenous DNA damage caused by both intrinsic and extrinsic stress. In this study, we demonstrate that the serial transplantation of human HSCs into immunodeficient mice triggers replication stress that induces incremental elevation of intracellular reactive oxygen species(ROS) levels and the accumulation of persistent DNA damage within the human HSCs. The study reveals that ROS play a causative role for DNA damage and the regulation of ROS have a major influence on human HSC aging.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (19 results)

All 2011 2010

All Journal Article (8 results) (of which Peer Reviewed: 7 results) Presentation (11 results)

  • [Journal Article] Accumulation of oxidative DNA damage restricts the self-renewal capacity of human hematopoietic stem cells2011

    • Author(s)
      Yahata T, Takanashi T, Muguruma Y, Ibrahim AA, Matsuzawa H, Uno T, Sheng Y, Onizuka M, Ito M, Kato S, Ando K
    • Journal Title

      Blood

      Volume: 118(11) Pages: 2941-50

    • NAID

      40019489714

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] MDS stem cells suppress normal hematopoiesis by niche invasion and microenvironment disruption2011

    • Author(s)
      Muguruma Y, Matsushita H, Yahata T, Yumino S, Tanaka Y, Miyachi H, Ogawa Y, Kawada H, Ito M, Ando K
    • Journal Title

      Haematologica

      Volume: 96(4) Pages: 543-51

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Accumulation of oxidative DNA damage restricts the self-renewal capacity of human hematopoietic stem cells2011

    • Author(s)
      Yahata, T.
    • Journal Title

      Blood

      Volume: 118 Issue: 11 Pages: 2941-2950

    • DOI

      10.1182/blood-2011-01-330050

    • NAID

      40019489714

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of xenograft model of human myelodysplastic syndromes2011

    • Author(s)
      Muguruma Y, Matsushita H, Yahata H, Yumino S, Tanaka Y, Miyachi H, Ogawa Y, Kawada H, Ito M, Ando K
    • Journal Title

      Haematologica

      Volume: 96 Issue: 4 Pages: 543-551

    • DOI

      10.3324/haematol.2010.027557

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adipocyte-derived mesenchymal stem cells facilitate hematopoiesis in vitro and in vivo : advantages over bone marrow-derived mesenchymal stem cells2010

    • Author(s)
      Nakao N, Nakayama T, Yahata T, Muguruma Y, Miyata Y, Naoe T
    • Journal Title

      Am J Pathol

      Volume: 117(2) Pages: 547-54

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of xenograft model of human myelodysplastic syndromes.2010

    • Author(s)
      Muguruma., et al
    • Journal Title

      Hematologica

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adipose tissue-derived mesenchymal stem cells facilitate hematopoiesis in vitro and in vivo : advantages over bone marrow-derived mesenchymal stem cells.2010

    • Author(s)
      Nakao N., et al.
    • Journal Title

      Am J Pathol.

      Volume: 177巻2号 Pages: 547-545

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 造血幹細胞ニッチ2010

    • Author(s)
      八幡崇
    • Journal Title

      Medical Science Digest

      Volume: 36巻6号 Pages: 2-4

    • Related Report
      2010 Annual Research Report
  • [Presentation] Klothoマウス敗血症モデルにおける免疫機能解析/Immune analysis of septic Klotho mice2011

    • Author(s)
      Inoue S., et al.
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ
    • Year and Date
      2011-11-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] APL mice model using PML-RARA-transduced CD34-positive hematopoietic cells from human cord blood2011

    • Author(s)
      Hiromichi Matsushita, Takashi Yahata, Yoshihiko Nakamura, Yin Sheng, Yukari Muguruma, Hideyuki Matsuzawa Tomoko Uno, Tomomi Takanashi, Tadayuki Sato, Masayuki Tanaka, Hideki Hayashi, Makoto Onizuka, Yoshiaki Ogawa, Hayato Miyachi, Kiyoshi Ando
    • Organizer
      第73回日本血液学会総会
    • Place of Presentation
      名古屋(名古屋国際会議場)
    • Year and Date
      2011-10-16
    • Related Report
      2011 Final Research Report
  • [Presentation] CD34+/CD38+ cells from human cord blood initiate APL by induction of PML-RARA2011

    • Author(s)
      Matsushita H., et al.
    • Organizer
      第73回日本血液学会学術集会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2011-10-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] Activation of Fibrinolytic Pathway Using a Novel Small Molecule Enhaneed Hematopoietic Regeneration2011

    • Author(s)
      Ibrahim Abd Aziz, et al.
    • Organizer
      第73回日本血液学会学術集会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2011-10-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Activation of Fibrinolytic Pathway Using a Novel Small Molecule Enhanced Hematopoietic Regeneration2011

    • Author(s)
      Abd Aziz Ibrahim, Takashi Yahata, Tomomi Takanashi, Toshio Miyata, and Kiyoshi Ando
    • Organizer
      第73回日本血液学会総会
    • Place of Presentation
      名古屋(名古屋国際会議場)
    • Year and Date
      2011-10-14
    • Related Report
      2011 Final Research Report
  • [Presentation] Notch signals regulate hematopoietic homeostasis through osteoblastic niche maintenance2010

    • Author(s)
      Yukari Muguruma, Takashi Yahata, Shizu Yumino, Yin Sheng, Katsuto Hozumi, Kiyoshi Ando
    • Organizer
      第72回日本血液学会総会
    • Place of Presentation
      神奈川(パシフィコ横浜)
    • Year and Date
      2010-09-24
    • Related Report
      2011 Final Research Report
  • [Presentation] Accumulation of DNA-damage limits the self-renewal capacity of human hematopoietic stem cells2010

    • Author(s)
      Takashi Yahata, Tomomi Takanashi, Hideyuki Matsuzawa, Yin Sheng, Tomoko Uno, Makoto Onizuka, Shunichi Kato, Kiyoshi Ando
    • Organizer
      第72回日本血液学会総会
    • Place of Presentation
      神奈川(パシフィコ横浜)
    • Year and Date
      2010-09-24
    • Related Report
      2011 Final Research Report
  • [Presentation] DNA損傷の蓄積はヒト造血幹細胞の自己複製能を制限する2010

    • Author(s)
      八幡崇
    • Organizer
      日本血液学会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] Notch signals regulate hematopoietic homeostasis through osteoblastic niche maintenance2010

    • Author(s)
      六車ゆかり
    • Organizer
      日本血液学会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] 骨芽細胞におけるDelta-like ligand1の発現が骨代謝維持に重要である2010

    • Author(s)
      六車ゆかり
    • Organizer
      日本骨代謝学会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Year and Date
      2010-07-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] DNA損傷の蓄積がヒト造血幹細胞の再生能力を低下させる2010

    • Author(s)
      八幡崇
    • Organizer
      日本サイトメトリー学会
    • Place of Presentation
      東京慈恵医科大学(東京都)
    • Year and Date
      2010-06-26
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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