DNA damage response in human hematopoietic stem cell

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790299
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Tokai 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
• Keywords: 再生医学

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.

Research Products

• [Journal Article] Accumulation of oxidative DNA damage restricts the self-renewal capacity of human hematopoietic stem cells (2011)
  • 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
  • Peer Reviewed
• [Journal Article] MDS stem cells suppress normal hematopoiesis by niche invasion and microenvironment disruption (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Adipocyte-derived mesenchymal stem cells facilitate hematopoiesis in vitro and in vivo : advantages over bone marrow-derived mesenchymal stem cells (2010)
  • 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
  • Peer Reviewed
• [Presentation] APL mice model using PML-RARA-transduced CD34-positive hematopoietic cells from human cord blood (2011)
  • 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
• [Presentation] Activation of Fibrinolytic Pathway Using a Novel Small Molecule Enhanced Hematopoietic Regeneration (2011)
  • 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
• [Presentation] Notch signals regulate hematopoietic homeostasis through osteoblastic niche maintenance (2010)
  • 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
• [Presentation] Accumulation of DNA-damage limits the self-renewal capacity of human hematopoietic stem cells (2010)
  • 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