Establishment of heredital desease models using iPS cells and genome editing

• Project/Area Number: 15H04286
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Kyoto University (2017); University of Miyazaki (2015-2016)
• Principal Investigator: Honda Arata 京都大学, 京都市, 特定准教授 (10373367)
• Co-Investigator(Kenkyū-buntansha): 下島 圭子 東京女子医科大学, 医学部, 特任助教 (30578935) ; 山海 直 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 霊長類医科学研究センター, 主任研究員 (80300937)
• Co-Investigator(Renkei-kenkyūsha): OGURA Atsuo 独立行政法人理化学研究所, バイオリソース研究センター, 室長 (20194524) ; MATSUDA Osamu 京都府立医科大学, 医学系研究科, 教授 (00271164)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000); Fiscal Year 2017: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000); Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2015: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: Experimental Animals / ES cells / iPS cells / naive / germ cells / chimera / iPS細胞 / ナイーブ変換 / キメラ / ゲノム編集 / 難治性疾患 / ES細胞 / ウサギ / カニクイザル

Outline of Final Research Achievements

This research project had been aimed for the establishment of heredital desease models using iPS cells and genome editing using several animal species. We achieved naive-like conversion of cynomolgus monkey ES/iPS cells, which can enhances their in vitro differentiation potential. Moreover, following mice and rats, the 3rd true naive-iPS cells were successfully established form an endangered species, Tokudaia osimensis. We produced interspecific chimera and elucidated the sexual plasticity of the germ cells of the endangered species.

Research Products

• [Journal Article] Applying iPSCs for preserving endangered species and elucidating the evolution of mammalian sex determination (2018)
  • Author(s): Arata Honda
  • Journal Title: BioEssays Volume: 印刷中 Issue: 6 Pages: 1700152-1700152
  • DOI: 10.1002/bies.201700152
  • Peer Reviewed / Open Access
• [Journal Article] Flexible adaptation of male germ cells from female iPSCs of endangered Tokudaia osimensis (2017)
  • Author(s): Arata Honda, Narantsog Choijookhuu, Haruna Izu, Yoshihiro Kawano, Mizuho Inokuchi, Kimiko Honsho, Ah-Reum Lee, Hiroki Nabekura, Hiroshi Ohta, Tomoyuki Tsukiyama, Yasuhide Ohinata, Asato Kuroiwa, Yoshitaka Hishikawa, Mitinori Saitou, Takamichi Jogahara, Chihiro Koshimoto
  • Journal Title: Science Advances Volume: - Issue: 5
  • DOI: 10.1126/sciadv.1602179
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Discrimination of stem cell status after subjecting cynomolgus monkey pluripotent stem cells to naive conversion. (2017)
  • Author(s): Honda A, Kawano Y, Izu H, Choijookhuu N, Honsho K, Nakamura T, Yabuta Y, Yamamoto T, Takashima Y, Hirose M, Sankai T, Hishikawa Y, Ogura A, Saitou M
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 45285-45285
  • DOI: 10.1038/srep45285
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Flexible adaptation of male germ cells from female iPS cells of endangered Tokudaia osimensis (2017)
  • Author(s): Arata Honda, Narantsog Choijookhuu, Haruna Izu, Yoshihiro Kawano, Mizuho Inokuchi, Kimiko Honsho, Ah-Reum Lee, Hiroki Nabekura, Hiroshi Ohta, Tomoyuki Tsukiyama, Yasuhide Ohinata, Asato Kuroiwa, Yoshitaka Hishikawa, Mitinori Saitou, Takamichi Jogahara, Chihiro Koshimoto.
  • Journal Title: Science Advances Volume: in press
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Flexible adaptation of male germ cells from female iPS cells of endangered Tokudaia osimensis (2017)
  • Author(s): Arata Honda, Narantsog Choijookhuu, Haruna Izu, Yoshihiro Kawano, Mizuho Inokuchi, Kimiko Honsho, Ah-Reum Lee, Hiroki Nabekura, Hiroshi Ohta, Tomoyuki Tsukiyama, Yasuhide Ohinata, Asato Kuroiwa, Yoshitaka Hishikawa, Mitinori Saitou, Takamichi Jogahara, and Chihiro Koshimoto
  • Journal Title: Science Advances Volume: in press
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CRISPR/Cas9-mediated genome editing in wild-derived mice: generation of tamed wild-derived strains by mutation of the a (nonagouti) gene (2017)
  • Author(s): Michiko Hirose, Ayumi Hasegawa, Keiji Mochida, Shogo Matoba, Yuki Hatanaka, Kimiko Inoue, Tatsuhiko Goto, Hideki Kaneda, Ikuko Yamada, Tamio Furuse, Kuniya Abe, Yoshihisa Uenoyama, Hiroko Tsukamura, Shigeharu Wakana, Arata Honda, and Atsuo Ogura
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 42476-42476
  • DOI: 10.1038/srep42476
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Calreticulin mutant mice develop essential thrombocythemia that is ameliorated by the JAK inhibitor ruxolitinib (2016)
  • Author(s): Kotaro Shide, Takuro Kameda, Takumi Yamaji, Masaaki Sekine, Naoki Inada, Ayako Kamiunten, Keiichi Akizuki, Kenichi Nakamura, Akira Kitanaka, Arata Honda, Akira Sawaguchi, Hiroo Abe, Tadashi Miike, Hisayoshi Iwakiri, Yoshihiro Tahara, Mitsue Sueta, Satoru Hasuike, Shojiro Yamamoto, Kenji Nagata, and Kazuya Shimoda
  • Journal Title: Leukemia Volume: 31 Issue: 5 Pages: 1136-1144
  • DOI: 10.1038/leu.2016.308
  • Peer Reviewed / Open Access
• [Journal Article] Expression of Six Proteins Causes Reprogramming of Porcine Fibroblasts Into Induced Pluripotent Stem Cells with Both Active X Chromosomes (2016)
  • Author(s): Tomokazu Fukuda, Tetsuya Tani, Seiki Haraguchi, Keichiro Donai, Nobuyoshi Nakajima, Hirohide Uenishi, Takahiro Eitsuka, Makoto Miyagawa, Sanghoun Song, Mananu Onuma, Yumi Hoshino, Eimei Sato, and Arata Honda.
  • Journal Title: J. Cell. Biochem. Volume: 118 Issue: 3 Pages: 537-553
  • DOI: 10.1002/jcb.25727
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 絶滅危惧種の特徴を iPS 細胞と発生工学で解き明かす (2018)
  • Author(s): 本多 新
  • Organizer: 関西実験動物研究会
  • Invited
• [Presentation] Germ Cells from Induced Pluripotent Stem Cells of an Endangered Species, Tokudaia Osimensis (2017)
  • Author(s): Arata Honda, Narantsog Choijookhuu, Haruna Izu, Yoshihiro Kawano, Yoshitaka Hishikawa, Takamichi Jogahara, Chihiro Koshimoto.
  • Organizer: Fourth World Congress of Reproductive Biology
  • Int'l Joint Research
• [Presentation] メスの細胞から精子｜性染色体XO型の絶滅危惧種アマミトゲネズミ細胞の性的柔軟性 (2017)
  • Author(s): 本多 新
  • Organizer: ConBio 2017
  • Invited
• [Presentation] iPS細胞と医療を繋ぐ (2017)
  • Author(s): 本多 新
  • Organizer: 日本看護遺伝学会第16回学術大会
  • Invited
• [Remarks] 宮崎大学テニュアトラック推進機構 本多研究室
  • URL: http://www.cc.miyazaki-u.ac.jp/maruhon/index.html