In vitro induction of totipotency from somatic cells in mice

• Project/Area Number: 25712030
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Animal production science
• Research Institution: Institute of Physical and Chemical Research (2013, 2016); University of Yamanashi (2014-2015)
• Principal Investigator: Ohinata Yasuhide 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 研究員 (70415107)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥25,350,000 (Direct Cost: ¥19,500,000、Indirect Cost: ¥5,850,000); Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
• Keywords: 胚性幹細胞 / 栄養膜幹細胞 / 胚盤胞 / 胚体外内胚葉幹細胞 / 全能性 / 発生・分化 / 幹細胞 / 生殖細胞 / iPS細胞 / 初期発生 / 多能性幹細胞

Outline of Final Research Achievements

High quality mouse naive ES/iPS cells can readily form tetraploid chimeras, which almost consist of donor pluripotent stem cells; however, these stem cells are not capable of developing embryos without using early embryos as host. To date, reconstruction of artificial embryos by stem cells in vitro has not been achieved. Progress has largely been impeded by our present lack of understanding and techniques. Within the research period, we reported novel pluripotent stem cells (intermediate pluripotent stem cells, INTPSCs) that improve the properties of stem cells, are maintained FGF dependently and have chimeric contribution ability and germline transmission ability. We also reported that establishment of trophoblast stem cells under chemically defined culture conditions.

Research Products

• [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] Generation of cloned mice and nuclear transfer embryonic stem cell lines from urine-derived cells. (2016)
  • Author(s): Mizutani E, Torikai K, Wakayama S, Nagatomo H, Ohinata Y, Kishigami S, Wakayama T.
  • Journal Title: Scientific Reports. Volume: 6 Issue: 1 Pages: 23808-23808
  • DOI: 10.1038/srep23808
  • NAID: 130007023594
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cellular dynamics of mouse trophoblast stem cells: Identification of a persistent stem cell type. (2016)
  • Author(s): Motomura K, Oikawa M, Hirose M, Honda A, Togayachi S, Miyoshi H, Ohinata Y, Sugimoto M, Abe K, Inoue K, Ogura A.
  • Journal Title: Biology of Reproduction Volume: 94 Issue: 6 Pages: 122-122
  • DOI: 10.1095/biolreprod.115.137125
  • Peer Reviewed / Open Access
• [Journal Article] A comprehensive system for generation and evaluation of induced pluripotent stem cells using piggyBac transposition (2014)
  • Author(s): Tsukiyama T, Kato-Itoh M, Nakauchi H, Ohinata Y
  • Journal Title: PLOS ONE Volume: 9 Issue: 3 Pages: e92973-e92973
  • DOI: 10.1371/journal.pone.0092973
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A modified EpiSC culture condition containing a GSK3 inhibitor can support germline-competent pluripotency in mice (2014)
  • Author(s): Tsukiyama T, Ohinata Y
  • Journal Title: PLOS ONE Volume: 9 Issue: 4 Pages: e95329-e95329
  • DOI: 10.1371/journal.pone.0095329
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Establishment of trophoblast stem cells under defined culture conditions in mice (2014)
  • Author(s): Ohinata Y, Tsukiyama T
  • Journal Title: PLOS ONE Volume: 9 Issue: 9 Pages: e107308-e107308
  • DOI: 10.1371/journal.pone.0107308
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Delivery of full-length factor VIII using a piggyBac transposon vector to correct a mouse model of hemophilia A (2014)
  • Author(s): Hideto Matsui, Naoko Fujimoto, Noriko Sasakawa, Yasuhide Ohinata, Midori Shima, Shinya Yamanaka, Mitsuhiko Sugimotom Akitsu Hotta
  • Journal Title: PLOS ONE Volume: 9(8) Issue: 8 Pages: e104957-e104957
  • DOI: 10.1371/journal.pone.0104957
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Reconstruction of the blastocyst by ES/iPS cells and TS cells in vitro (2016)
  • Author(s): Yasuhide Ohinata, Eriko Sano, Kana Kishida, Hiroaki Nagatomo, Eiji Mizutani, Teruhiko Wakayama
  • Organizer: International symposium on the future of nuclear transfer and nuclear reprogamming
  • Place of Presentation: University, Yamanashi
  • Year and Date: 2016-03-10
  • Int'l Joint Research
• [Patent(Industrial Property Rights)] 栄養膜外胚葉様構造体及び製造方法 (2015)
  • Inventor(s): 大日向康秀
  • Industrial Property Rights Holder: 国立研究開発法人理化学研究所
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-102260
  • Filing Date: 2015-05-19
• [Patent(Industrial Property Rights)] 栄養膜幹細胞の樹立及び維持方法 (2014)
  • Inventor(s): 大日向康秀
  • Industrial Property Rights Holder: 理化学研究所
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-032314
  • Filing Date: 2014-02-21