Functional analysis of RPL5 using induced pluripotent stem cells from the patient with Diamond-Blackfan Anemia

• Project/Area Number: 17K17323
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Okayama University
• Principal Investigator: Hayano Satoru 岡山大学, 大学病院, 講師 (20633712)
• Research Collaborator: SHIMADA Akira ; SAITO Megumu ; KAMIOKA Hiroshi ; KAWANABE Noriaki ; Fukui Yuko
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ダイアモンド・ブラックファン貧血 / RPL5 / iPS細胞 / 細胞・組織 / 発生・分化

Outline of Final Research Achievements

In this study, we focused on Diamond-Blackfan anemia (DBA), which is characterized by red blood cell aplasia and craniofacial defects. iPS cells derived from DBA patient was used in this study. Our current study indicates that craniofacial defect is caused by activation of p53-mediated cell death pathway which is induced by interaction between ribosomal proteins and MDM2.

Academic Significance and Societal Importance of the Research Achievements

クルーゾンシンドロームや外胚葉異形成症など、発生率が比較的高い疾患においては、モデルマウスなどを用いた研究によりその発症機構が明らかになりつつあるが、大部分の頭蓋顔面の形態異常を伴う先天性疾患については、未だその発生機構が解明されていない。今回我々は患者由来の細胞から樹立したiPS細胞を用い、頭蓋顔面形態異常を伴う、ダイアモンドブラックファン貧血における骨格的フェノタイプの発症機構を解明した。本方法を用いることにより、未だに解明されていない多くの先天性疾患の分子メカニズムを解明することが期待される。

Research Products

• [Journal Article] Role of the Inferior Alveolar Nerve in Rodent Lower Incisor Stem Cells. (2018)
  • Author(s): Satoru Hayano, Yuko Fukui, Noriaki Kawanabe, Kana, Kono, Masahiro Nakamura, Yoshihito Ishihara, Hiroshi Kamioka
  • Journal Title: Journal of Dental Research Volume: 印刷中 Issue: 8 Pages: 954-961
  • DOI: 10.1177/0022034518758244
  • Peer Reviewed
• [Journal Article] Compound mutations in Bmpr1a and Tak1 synergize facial deformities via increased cell death (2018)
  • Author(s): Xia Liu, Satoru Hayano, Haichun Pan, Maiko Inagaki, Jun Ninomiya-Tsuji, Hongchen Sun, Yuji Mishina
  • Journal Title: Genesis Volume: 56 Issue: 3
  • DOI: 10.1002/dvg.23093
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Rapamycin rescues BMP mediated midline craniosynostosis phenotype through reduction of mTOR signaling in a mouse model (2018)
  • Author(s): Kramer K, Yang J, Swanson WB, Hayano S, Toda M, Pan H, Kim JK, Krebsbach PH, Mishina Y
  • Journal Title: Genesis Volume: 56 Issue: 6-7
  • DOI: 10.1002/dvg.23220
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Role of Osteocyte-PDL Crosstalk in Tooth Movement via SOST/Sclerostin (2018)
  • Author(s): Odagaki N, Ishihara Y, Wang Z, Ei Hsu Hlaing E, Nakamura M, Hoshijima M, Hayano S, Kawanabe N, Kamioka H.
  • Journal Title: J Dent Res Volume: in press Issue: 12 Pages: 1374-1382
  • DOI: 10.1177/0022034518771331
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Relation between chondrodysplasia and RPL5-associated cell death in Diamond-Blackfan Anemia (2019)
  • Author(s): Yuko Fukui, Satoru Hayano, Megumu Saito, Akira Shimada, Noriaki Kawanabe, Hiroshi Kamioka
  • Organizer: 第32回日本軟骨代謝学会
• [Presentation] Role of the inferior alveolar nerve in the mesenchymal stem/progenitor cells (2018)
  • Author(s): Satoru Hayano, Noriaki Kawanabe, Yuko Fukui, Hiroshi Kamioka
  • Organizer: 94th European Orthodontic Society Congress
  • Int'l Joint Research
• [Presentation] 歯根膜の圧迫負荷は骨細胞のSOST/Sclerostinを介した歯槽骨代謝制御をパラクライン機構によって調節する (2018)
  • Author(s): 小田垣直弥，石原嘉人，王紫儀，イイスライン，中村政裕，星島光博，早野暁，川邉紀章，上岡寛
  • Organizer: 第77回日本矯正歯科学会学術大会