Functional regulation and producion for next-generation of mesenchymal stem cells

2018 Fiscal Year Annual Research Report

• Project/Area Number: 16K10376
• Research Institution: Yamagata University
• Principal Investigator: 田嶋 克史 山形大学, 医学部, 非常勤講師 (80292423)
• Co-Investigator(Kenkyū-buntansha): 富山 健一 国立研究開発法人国立精神・神経医療研究センター, 精神保健研究所 薬物依存研究部, 科研費研究員 (20584064) ; 滝澤 和也 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 放射線障害治療研究部, 研究員(任非) (20739388) ; 安田 武嗣 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 放射線障害治療研究部, 主任研究員(定常) (60332269) ; 小原 千寿香 (逸見千寿香) 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 放射線障害治療研究部, 主任研究員(任非) (90415977)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: mesenchyma stem cells / iPSCs / RAD52 / double-strand breaks / homologous recombination / acetylation

Outline of Annual Research Achievements

The generation of induced-pluripotential stem cells (iPSCs)-derived mesenchymal stem cells (iMSCs) is an attractive and promising approach for preparing large, uniform batches of applicable MSCs that can serve as an alternative cell source of primary MSCs. Appropriate culture surfaces may influence their growth and differentiation potentials during iMSC derivation. In the present study, we established the simple and effective derivation method for mouse iMSCs using extracellular component as gelatin.
MSCs are generally resistant to DNA damages including radiation. However, the underlying mechanisms remained unclear. Thus, we investigated how MSCs repair DNA damages including DNA double strand breaks (DSBs). We found that p300/CBP acetylate human RAD52 at DSB sites. An immunofluorescence microscopy analysis revealed that non-acetylated RAD52 mutants initially accumulates at DSB sites, but dissociates prematurely from them. In the absence of RAD52 acetylation, RAD51, which plays a central role in homologous recombination (HR), also dissociates prematurely from DSB sites, and hence HR is impaired. Furthermore, we found that the acetylation of RAD52 at DSB sites is dependent on the ATM protein kinase activity, through the formation of RAD52 and p300/CBP foci at DSB sites. Our findings clarify the importance of RAD52 acetylation in HR of MSCs

Research Products

• [Journal Article] Giant cellulitis-like Sweet syndrome as an initial clinical presentation of acute myeloblastic leukemia with t(6;9)(p23;q34): DEK-CAN and internal duplications of FMS-like tyrosine kinase 3 (2019)
  • Author(s): Okuyama Shuhei、Nito Toshiya、Yanagawa Naoki、Tajima Katsushi
  • Journal Title: Annals of Hematology Volume: 98 Pages: 787～788
  • DOI: 10.1007/s00277-019-03613-1
  • Peer Reviewed
• [Journal Article] MultiSite Gateway Technology Is Useful for Donor DNA Plasmid Construction in CRISPR/Cas9-Mediated Knock-In System (2018)
  • Author(s): Yasuda Takeshi、Tajima Katsushi
  • Journal Title: IntechOpen Volume: 2 Pages: 1-21
  • Peer Reviewed / Open Access
• [Journal Article] Nocardia otitidiscaviarum meningitis in a diffuse large B-cell lymphoma patient with CD4-positive lymphocytopenia and persistent oligoclonal CD8-positive lymphocytes in the peripheral blood (2018)
  • Author(s): Katsushi Tajima, Taichi Terada, Shuhei Okuyama, Daisuke Akaneya, Ryuichiro Hori, Shuichi Abe, Mitsumasa Osakabe, Hiroaki Kumagai1, Riko Tsumanuma1, Eijiro Omoto, Junko Ito6, Tohru Gonoi
  • Journal Title: Int J Clin Exp Pathol Volume: 11 Pages: 455-461
  • Peer Reviewed / Open Access