Analysis of disease mechanism of growth impairment in Down syndrome using human iPS cells

• Project/Area Number: 25461643
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Osaka University
• Principal Investigator: ARAHORI HITOMI 大阪大学, 医学(系)研究科(研究院), 助教 (40379186)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 成長障害 / 軟骨細胞 / ダウン症候群 / iPS細胞 / ゲノム編集 / 染色体異常症候群

Outline of Final Research Achievements

Down syndrome (DS) is the most common chromosomal aneuploidy, which is caused by the trisomy of chromosome 21. Among their various medical symptom, DS patients show impairment in the growth. To analyze the mechanism of this growth impairment in DS, we generated DS-specific human induced pluripotent stem cells (iPSCs) from the cord blood using Sendaivirus vector, and differentiated them to chondrocyte. Although chondrocyte was successfully differentiated from human iPSC, its percentage was not sufficient yet. On the other hand, fibroblasts derived from not only DS patients but also 13, 18 trisomy patients showed low proliferation rate and premature senescence. The premature senescence was accompanied by accelerated RNA / protein synthesis, followed by increased oxidative stress. This trisomy-induced stress can be a major cause of growth impairment in DS.

Research Products

• [Journal Article] Systematic cellular disease models reveal synergistic interactions of trisomy 21 and GATA1 mutations in hematopoietic abnormalities (2016)
  • Author(s): K. Banno, S. Omori, K. Hirata, N. Nawa, N. Nakagawa, K. Nishimura, M. Ohtaka, M. Nakanishi, T. Sakuma, T. Yamamoto, T. Toki, E. Ito, T. Yamamoto, C. Kokubu, J. Takeda, H. Taniguchi, H. Arahori, K. Wada, Y. Kitabatake and K. Ozono
  • Journal Title: Cell Reports Volume: 15 Issue: 6 Pages: 1-15
  • DOI: 10.1016/j.celrep.2016.04.031
  • NAID: 120007135439
  • Peer Reviewed / Open Access
• [Presentation] ダウン症候群における病態発症メカニズムの解明 (2014)
  • Author(s): 北畠 康司、坂野 公彦、平田 克弥、大森 早也佳、荒堀 仁美、松浪 桂、谷口 英俊、和田 和子、大薗 恵一
  • Organizer: 第117回日本小児科学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-04-11
• [Presentation] 疾患特異的ヒトiPS細胞をもちいたダウン症候群の病態解析 (2014)
  • Author(s): 北畠 康司、坂野 公彦、大森 早也佳、平田 克弥、那波 伸敏、和田 和子、荒堀 仁美、谷口 英俊、大薗 恵一
  • Organizer: 第37回日本小児遺伝学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-04-10