Elucidation of the mechanisms of organ size determination

• Project/Area Number: 26460358
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Yamaguchi Tomoyuki 東京大学, 医科学研究所, 特任准教授 (80392158)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 臓器サイズ / 胚盤胞補完法 / 異種動物 / 異種胚盤胞補完法 / 異種キメラ / 臓器サイズ制御 / Hippo pathway

Outline of Final Research Achievements

In order to understand the mechanisms of determination of the size of body or the organ, - specifically, whether that is controlled by intrinsic or extrinsic cues, we performed interspecies blastocyst complementation. As a result, the size of mouse pancreas generated in rat was rat size (about ten times larger than mouse pancreas). This result indicate that the extrinsic signal as well as intrinsic signal is important for the organ size determination.

Research Products

• [Int'l Joint Research] Stanford university(USA)
• [Journal Article] Interspecies organogenesis generates autologous functional islets. (2017)
  • Author(s): Yamaguchi T, Sato H, Kato-Itoh M, Goto T, Hara H, Sanbo M, Mizuno N, Kobayashi T, Yanagida A, Umino A, Ota Y, Hamanaka S, Masaki H, Rashid ST, Hirabayashi M, Nakauchi H.
  • Journal Title: Nature. Volume: 542(7640) Pages: 191-196
  • DOI: 10.1038/nature21070
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Inhibition of Apoptosis Overcomes Stage-Related Compatibility Barriers to Chimera Formation in Mouse Embryos. (2016)
  • Author(s): Masaki H, Kato-Itoh M, Takahashi Y, Umino A, Sato H, Ito K, Yanagida A, Nishimura T, Yamaguchi T, Hirabayashi M, Era T, Loh KM, Wu SM, Weissman IL, Nakauchi H.
  • Journal Title: Cell Stem Cell. Volume: 19(5) Pages: 587-592
  • DOI: 10.1016/j.stem.2016.10.013
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Practical selection methods for rat and mouse round spermatids without DNA staining by flow cytometric cell sorting. (2016)
  • Author(s): Hayama T, Yamaguchi T, Kato-Itoh M, Ishii Y, Mizuno N, Umino A, Sato H, Sanbo M, Hamanaka S, Masaki H, Hirabayashi M, Nakauchi H.
  • Journal Title: Mol Reprod Dev. Volume: 83(6) Pages: 488-96
  • DOI: 10.1002/mrd.22644
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Matrix metalloproteinase-14 mediates formation of bile ducts and hepatic maturation of fetal hepatic progenitor cells. (2016)
  • Author(s): Otani S, Kakinuma S, Kamiya A, Goto F, Kaneko S, Miyoshi M, Tsunoda T, Asano Y, Kawai-Kitahata F, Nitta S, Nakata T, Okamoto R, Itsui Y, Nakagawa M, Azuma S, Asahina Y, Yamaguchi T, Koshikawa N, Seiki M, Nakauchi H, Watanabe M.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 469 Pages: 1062-1068
  • DOI: 10.1016/j.bbrc.2015.12.105
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Investigation of bi-potent differentiation of hepatoblasts using inducible diphtheria toxin receptor-transgenic mice. (2016)
  • Author(s): Yanagida A, Mizuno N, Yamazaki Y, Kato-Itoh M, Umino A, Sato H, Ito K, Yamaguchi T, Nakauchi H, Kamiya A.
  • Journal Title: Hepatol Research Volume: Nov 19. Pages: 816-828
  • DOI: 10.1111/hepr.12622
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] An assessment of the effects of ectopic gp91phox expression in XCGD iPSC-derived neutrophils. (2015)
  • Author(s): Lin HT, Masaki H, Yamaguchi T, Wada T, Yachie A, Nishimura K, Ohtaka M, Nakanishi M, Nakauchi H, Otsu M.
  • Journal Title: Mol. Ther. Methods Clin. Dev. Volume: 2 Pages: 15046-15046
  • DOI: 10.1038/mtm.2015.46
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Safeguard System for Induced Pluripotent Stem Cell Derived Rejuvenated T Cell Therapy (2015)
  • Author(s): Ando M, Nishimura T, Yamazaki S, Yamaguchi T, Kawana-Tachikawa A, Hayama T, Nakauchi Y, Ando J, Ota Y, Takahashi S, Nishimura K, Ohtaka M, Nakanishi M, Miles JJ, Burrows SR, Brenner MK, Nakauchi H.
  • Journal Title: Stem Cell Repots Volume: 5(4) Pages: 597-608
  • DOI: 10.1016/j.stemcr.2015.07.011
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Interspecific in vitro assay for chimera-forming ability of human pluripotent stem cells. (2015)
  • Author(s): Masaki H, Kato-Itoh M, Umino A, Sato H, Hamanaka S, Kobayashi T, Yamaguchi T, Nishimura K, Ohtaka M, Nakanishi M, Nakauchi H.
  • Journal Title: Development Volume: 142(18) Pages: 3222-30
  • DOI: 10.1242/dev.124016
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Liver maturation deficiency in p57(Kip2)-/- mice occurs in a hepatocytic p57(Kip2) expression-independent manner (2015)
  • Author(s): agida A, Chikada H, Ito K, Umino A, Kato-Itoh M, Yamazaki Y, Sato H, Kobayashi T, Yamaguchi T, Nakayama KI, Nakauchi H, Kamiya A.
  • Journal Title: Dev. Biol. Volume: 407(2) Pages: 331-343
  • DOI: 10.1016/j.ydbio.2015.07.004
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Successful Reprogramming of Epiblast Stem Cells by Blocking Nuclear Localization of β-Catenin. (2015)
  • Author(s): Murayama H, Masaki H, Sato H, Hayama T, Yamaguchi T, Nakauchi H
  • Journal Title: Stem Cell Reports. Volume: 4 Pages: 103-13
  • DOI: 10.1016/j.stemcr.2014.12.003
  • Peer Reviewed / Open Access
• [Journal Article] The generation and maintenance of rat induced pluripotent stem cells. (2014)
  • Author(s): Hayama T, Yamaguchi T, Kato-Itoh M, Hamanaka S, Kawarai M, Sanbo M, Tamura C, Lee YS, Yanagida A, Murayama H, Mizuno N, Umino A, Sato H, Yamazaki S, Masaki H, Kobayashi T, Hirabayashi M, Nakauchi H
  • Journal Title: Methods Mol Biol. Volume: 91(4) 89 Pages: 143-50
  • DOI: 10.1095/biolreprod.114.121640
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 異種動物個体内での膵臓再生と膵島移植 (2017)
  • Author(s): 山口智之
  • Organizer: 第44回膵・膵島移植研究会
  • Place of Presentation: 京都
  • Year and Date: 2017-03-11
• [Presentation] 異種環境内における多能性幹細胞の発生限界 (2017)
  • Author(s): 山口智之
  • Organizer: 第16回日本再生医療学会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-09
• [Presentation] 動物個体内での膵臓の再生 (2016)
  • Author(s): 山口智之
  • Organizer: 第59回日本糖尿病学会年次学術集会
  • Place of Presentation: 京都
  • Year and Date: 2016-05-21
• [Presentation] 異種体内で作製した膵島の移植による長期血糖値制御 (2016)
  • Author(s): 山口智之
  • Organizer: 第15回日本再生医療学会総会
  • Place of Presentation: 大阪国際会議場 （大阪府大阪市）
  • Year and Date: 2016-03-18
• [Presentation] 異種動物体内でのiPS細胞からの膵臓作製 (2015)
  • Author(s): 山口智之
  • Organizer: 第１０回信州肝胆膵外科先端医療研究会
  • Place of Presentation: ホテルブエナビスタ（長野県松本市）
  • Year and Date: 2015-12-05
  • Invited
• [Presentation] 多能性幹細胞の異種環境における発生限界 (2015)
  • Author(s): 山口智之
  • Organizer: BMB2015（第38回日本分子生物学会年会・第88回日本生化学会大会 合同大会）
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] 動物個体内での膵臓の再生 (2015)
  • Author(s): 山口智之
  • Organizer: 第101回日本消化器病学会総会
  • Place of Presentation: 仙台 国際センター （宮城県仙台市）
  • Year and Date: 2015-04-24
  • Invited
• [Book] 組織工学ライブラリ (2016)
  • Author(s): 山口智之
  • Total Pages: 250
  • Publisher: コロナ社
• [Book] 臨床薬学テキストシリーズ (2016)
  • Author(s): 山口智之
  • Total Pages: 283
  • Publisher: 中山書店
• [Book] Hyper Bio Assembler for 3D Cellular Systems. (2015)
  • Author(s): Iriguchi S, Yamaguchi T
  • Total Pages: 78
  • Publisher: Springer
• [Book] 三次元ティッシュエンジニアリング (2015)
  • Author(s): 山口智之
  • Total Pages: 6
  • Publisher: 株式会社エヌ・ティー・エス
• [Book] 最新医学 (2014)
  • Author(s): 山口智之、中内啓光
  • Total Pages: 10
  • Publisher: 最新医学社
• [Book] 医学のあゆみ (2014)
  • Author(s): 山口智之
  • Total Pages: 1
  • Publisher: 医歯薬出版株式会社