Functional analysis of stem cell glycans and development of novel glycan engineering technologies for regenerative medicine

• Project/Area Number: 25712039
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Applied molecular and cellular biology
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: Tateno Hiroaki 国立研究開発法人産業技術総合研究所, 創薬基盤研究部門, 主任研究員 (30450670)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000); Fiscal Year 2015: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000); Fiscal Year 2014: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000); Fiscal Year 2013: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
• Keywords: 糖鎖 / レクチン / 幹細胞 / 再生医療 / 腫瘍

Outline of Final Research Achievements

hiPSCs and hESCs have abilities to proliferate eternally (self-renewal) and differentiate into any cell types such as cardiomyocytes and neurons (pluripotency). Therefore, hiPSCs and hESCs gain a lot of attentions as cell sources for regenerative medicine. I have discovered a hiPSC/hESC-specific lectin called rBC2LCN. In this study, I analyzed the binding mechanisms of rBC2LCN to hiPSCs/hESCs, clarified the functions of glycans recognized by the lectin, and developed technologies to detect and eliminate undifferentiated cells.

Research Products

• [Journal Article] Cell surface localization of importin α1/KPNA2 affects cancer cell proliferation by regulating FGF1 signalling. (2016)
  • Author(s): Yamada K., Miyamoto Y., Tsujii A., Moriyama T., Ikuno Y., Shiromizu T., Serada S., Fujimoto M., Tomonaga T., Naka T., Oka M.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 24823-24823
  • DOI: 10.1038/srep24823
  • Peer Reviewed / Open Access
• [Journal Article] Mutated leguminous lectin containing a heparin-binding like motif in a carbohydrate-binding loop specifically binds to heparin (2015)
  • Author(s): Abo, H. , Soga, K., Tanaka, A., Tateno, H., Hirabayashi, J., Yamamoto, K
  • Journal Title: PLoS One Volume: 10 Issue: 12 Pages: 1-13
  • DOI: 10.1371/journal.pone.0145834
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mammalian Cell Surface Display as a Novel Method for Developing Engineered Lectins with Novel Characteristics. (2015)
  • Author(s): Soga K, Abo H, Qin SY, Kyoutou T, Hiemori K, Tateno H, Matsumoto N, Hirabayashi J, Yamamoto K
  • Journal Title: Biomolecules Volume: 5 Issue: 3 Pages: 1540-1562
  • DOI: 10.3390/biom5031540
  • Peer Reviewed / Open Access
• [Journal Article] Effects of Hemagglutination Activity in the Serum of a Deep-Sea Vent Endemic Crab, <i>Shinkaia Crosnieri</i>, on Non-Symbiotic and Symbiotic Bacteria (2015)
  • Author(s): So Fujiyoshi, Hiroaki Tateno, Tomoo Watsuji, Hideyuki Yamaguchi, Daisuke Fukushima, Sayaka Mino, Makoto Sugimura, Tomoo Sawabe, Ken Takai, Shigeki Sawayama, Satoshi Nakagawa
  • Journal Title: Microbes and Environments Volume: 30 Issue: 3 Pages: 228-234
  • DOI: 10.1264/jsme2.ME15066
  • NAID: 130005099200
  • ISSN: 1342-6311, 1347-4405
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Lectin Engineering, a Molecular Evolutionary Approach to Expanding the Lectin Utilities (2015)
  • Author(s): Hu D, Tateno H, Hirabayashi J
  • Journal Title: Molecules Volume: 20 Issue: 5 Pages: 7637-7656
  • DOI: 10.3390/molecules20057637
  • Peer Reviewed / Open Access
• [Journal Article] A Novel Probe as Surface Glycan Marker of Pluripotent Stem Cells: Research Outcomes and Application to Regenerative Medicine. (2015)
  • Author(s): Hirabayashi J, Tateno H, Onuma Y, Ito Y
  • Journal Title: Adv Healthc Mater. Volume: なし Issue: 16 Pages: 2520-2529
  • DOI: 10.1002/adhm.201400837
  • Peer Reviewed
• [Journal Article] Mannose-recognition mutant of the galactose/N-acetylgalactosamine-specific C-type lectin CEL-I engineered by site-directed mutagenesis (2015)
  • Author(s): Moriuchi H, Unno H, Goda S, Tateno H, Hirabayashi J, Hatakeyama T
  • Journal Title: Biochim Biophys Acta Volume: 1850 Issue: 7 Pages: 1457-1465
  • DOI: 10.1016/j.bbagen.2015.04.004
  • Peer Reviewed
• [Journal Article] Elimination of Tumorigenic Human Pluripotent Stem Cells by a Recombinant Lectin-Toxin Fusion Protein (2015)
  • Author(s): Tateno H, Onuma Y, Ito Y, Minoshima F, Saito S, Shimizu M, Aiki Y, Asashima M, Hirabayashi J
  • Journal Title: Stem Cell Reports Volume: 4 Issue: 5 Pages: 1-10
  • DOI: 10.1016/j.stemcr.2015.02.016
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Development and Applications of the Lectin Microarray (2015)
  • Author(s): Hirabayashi J, Kuno A, Tateno H
  • Journal Title: Top Curr Chem Volume: 367 Pages: 105-124
  • DOI: 10.1007/128_2014_612
  • ISBN: 9783319213163, 9783319213170
  • Peer Reviewed
• [Journal Article] Engineering of a 3'-sulpho-Galβ1-4GlcNAc-specific probe by a single amino acid substitution of a fungal galectin (2015)
  • Author(s): Hu D, Huang H, Tateno H, Nakakita S, Sato T, Narimatsu H, Yao X, Hirabayashi J
  • Journal Title: J Biochem Volume: 157 Issue: 4 Pages: 197-200
  • DOI: 10.1093/jb/mvv023
  • Peer Reviewed
• [Journal Article] S-nitrosylation of mouse galectin-2 prevents oxidative inactivation by hydrogen peroxide (2015)
  • Author(s): Tamura M, Saito M, Yamamoto K, Takeuchi T, Ohtake K, Tateno H, Hirabayashi J, Kobayashi J, Arata Y
  • Journal Title: Biochem Biophys Res Commun Volume: 457 Issue: 4 Pages: 712-717
  • DOI: 10.1016/j.bbrc.2015.01.055
  • NAID: 120005575972
  • Peer Reviewed
• [Journal Article] Isolation and Biochemical Characterization of Apios Tuber Lectin (2015)
  • Author(s): Eri Kenmochi, Syed Rashel Kabir, Tomohisa Ogawa, Ryno Naude, Hiroaki Tateno, Jun Hirabayashi and Koji Muramoto
  • Journal Title: Molecules Volume: 20 Issue: 1 Pages: 987-1002
  • DOI: 10.3390/molecules20010987
  • Peer Reviewed / Open Access
• [Journal Article] The Lectin Frontier Database (LfDB), and data generation based on frontal affinity chromatography (2015)
  • Author(s): Hirabayashi J, Tateno H, Shikanai T, Aoki-Kinoshita KF, Narimatsu H
  • Journal Title: Molecules Volume: 20 Issue: 1 Pages: 951-973
  • DOI: 10.3390/molecules20010951
  • Peer Reviewed / Open Access
• [Journal Article] A C-type lectin isolated from the skin of Japanese bullhead shark (Heterodontus japonicus) binds a remarkably broad range of sugars and induces blood coagulation (2015)
  • Author(s): Tsutsui S, Dotsuta Y, Ono A, Suzuki M, Tateno H, Hirabayashi J, Nakamura O
  • Journal Title: J Biochem Volume: 157 Issue: 5 Pages: 345-356
  • DOI: 10.1093/jb/mvu080
  • Peer Reviewed
• [Journal Article] Molecular clock regulates daily α1-2-fucosylation of the neural cell adhesion molecule (NCAM) within mouse secondary olfactory neurons (2014)
  • Author(s): Kondoh D, Tateno H, Hirabayashi J, Yasumoto Y, Nakao R, Oishi K
  • Journal Title: J Biol Chem Volume: 289 Issue: 12 Pages: 36158-36165
  • DOI: 10.1080/09168451.2014.948376
  • Peer Reviewed
• [Journal Article] Lectin structures: classification based on the 3-D structures (2014)
  • Author(s): Fujimoto Z, Tateno H, Hirabayashi J
  • Journal Title: Methods Mol Biol Volume: 1200 Pages: 579-606
  • DOI: 10.1007/978-1-4939-1292-6_46
  • ISBN: 9781493912919, 9781493912926
• [Journal Article] Comprehensive list of lectins: origins, natures, and carbohydrate specificities (2014)
  • Author(s): Kobayashi, Y, Tateno, H, Ogawa, H, Yamamoto, K, Hirabayashi, J.
  • Journal Title: Methods Mol. Biol. Volume: 1200 Pages: 555-577
  • DOI: 10.1007/978-1-4939-1292-6_45
  • ISBN: 9781493912919, 9781493912926
• [Journal Article] Directed evolution of lectins by an improved error-prone PCR and ribosome display method (2014)
  • Author(s): Hu D, Tateno H, Hirabayashi J
  • Journal Title: Methods Mol Biol Volume: 1200 Pages: 527-538
  • DOI: 10.1007/978-1-4939-1292-6_43
  • ISBN: 9781493912919, 9781493912926
• [Journal Article] Evaluation of glycan-binding specificity by glycoconjugate microarray with an evanescent-field fluorescence detection system (2014)
  • Author(s): Tateno H
  • Journal Title: Methods Mol Biol Volume: 1200 Pages: 353-359
  • DOI: 10.1007/978-1-4939-1292-6_30
  • ISBN: 9781493912919, 9781493912926
• [Journal Article] Live-cell imaging of human pluripotent stem cells by a novel lectin probe rBC2LCN (2014)
  • Author(s): Tateno H, Onuma Y, Ito Y
  • Journal Title: Methods Mol Biol Volume: 1200 Pages: 313-318
  • DOI: 10.1007/978-1-4939-1292-6_26
  • ISBN: 9781493912919, 9781493912926
• [Journal Article] Application of lectin microarray to bacteria including Lactobacillus casei/paracasei strains (2014)
  • Author(s): Yasuda E, Sako T, Tateno H, Hirabayashi J
  • Journal Title: Methods Mol Biol Volume: 1200 Pages: 295-311
  • DOI: 10.1007/978-1-4939-1292-6_25
  • ISBN: 9781493912919, 9781493912926
• [Journal Article] A medium hyperglycosylated podocalyxin enables noninvasive and quantitative detection of tumorigenic human pluripotent stem cells (2014)
  • Author(s): Tateno H, Onuma Y, Ito Y, Hiemori K, Aiki Y, Shimizu M, Higuchi K, Fukuda M, Warashina M, Honda S, Asashima M, Hirabayashi J.
  • Journal Title: Scientific Reports Volume: 4 Issue: 1 Pages: 4069-4069
  • DOI: 10.1038/srep04069
  • Peer Reviewed
• [Journal Article] 先端糖鎖プロファイリング技術による新規未分化細胞マーカーの発見とレクチン育種 (2014)
  • Author(s): 平林淳、舘野浩章
  • Journal Title: 化学と生物 Volume: 52 Pages: 40-47
  • NAID: 40019936731
• [Journal Article] Terminal N-acetylgalactosamine-specific leguminous lectin from Wisteria japonica as a probe for human lung squamous cell carcinoma. (2013)
  • Author(s): Soga et al.
  • Journal Title: PLoS ONE Volume: 8(12) Issue: 12 Pages: e83886-e83886
  • DOI: 10.1371/journal.pone.0083886
  • Peer Reviewed
• [Journal Article] Conformational change of a unique sequence in a fungal galectin from Agrocybe cylindracea controls glycan ligand-binding specificity (2013)
  • Author(s): Kuwabara N, Hu D, Tateno H, Makyio H, Hirabayashi J, Kato R
  • Journal Title: FEBS Letter Volume: 587 Issue: 22 Pages: 3620-3625
  • DOI: 10.1016/j.febslet.2013.08.046
  • Peer Reviewed
• [Journal Article] Tailoring GalNAcα1-3Galβ-specific lectins from a multi-specific fungal galectin: dramatic change of carbohydrate specificity by a single amino-acid substitution (2013)
  • Author(s): Hu D, Tateno H, Sato T, Narimatsu H, Hirabayashi J
  • Journal Title: Biochemical Journal Volume: 453 Issue: 2 Pages: 261-270
  • DOI: 10.1042/bj20121901
  • Peer Reviewed
• [Journal Article] Podocalyxin Is a Glycoprotein Ligand of the Human Pluripotent Stem Cell-Specific ProberBC2LCN. (2013)
  • Author(s): Tateno H, Matsushima A, Hiemori K, Onuma Y, Ito Y, Hasehira K, Nishimura K,Ohtaka M, Takayasu S, Nakanishi M, Ikehara Y,Nakanishi M, Ohnuma K, Chan T,Toyoda M, Akutsu H, Umezawa A, Asashima M, Hirabayashi J.
  • Journal Title: Stem Cells Transl Med. Volume: 2(4) Issue: 4 Pages: 265-273
  • DOI: 10.5966/sctm.2012-0154
  • Peer Reviewed
• [Journal Article] 特異的レクチンを利用したヒト幹細胞の簡便な品質管理法の開発 (2013)
  • Author(s): 伊藤弓弦、舘野浩章、小沼泰子、平林淳
  • Journal Title: バイオサイエンスとインダストリー(B&I) Volume: 71 Pages: 432-433
  • NAID: 10031192977
• [Journal Article] ヒトiPS・ES細胞特異的プローブrBC2LCNの開発 (2013)
  • Author(s): 舘野浩章
  • Journal Title: 和光純薬時報 Volume: 81 Pages: 2-3
• [Journal Article] The Cellular Glycome of Human Induced Pluripotent Stem Cells and Their Specific Probe rBC2LCN (2013)
  • Author(s): 舘野浩章、平林淳
  • Journal Title: TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY Volume: 26 Pages: 1-35
• [Presentation] Detection and elimination of human pluripotent stem cells residing in cell therapy (2016)
  • Author(s): 舘野浩章・小沼泰子・伊藤弓弦・浅島誠・平林淳
  • Organizer: CiRA/ISSCR 2016 International Symposium
  • Place of Presentation: 京都大学
  • Year and Date: 2016-03-22
  • Int'l Joint Research
• [Presentation] 培養液を用いたin vitro造腫瘍性試験の開発 (2016)
  • Author(s): 舘野浩章
  • Organizer: 第15回日本再生医療学会総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2016-03-19
  • Invited
• [Presentation] 薬剤融合型レクチン(rBC2LCN-PE23)によるヒトiPS/ES細胞除去技術の (2016)
  • Author(s): 舘野浩章・小沼泰子・伊藤弓弦・浅島誠・平林淳
  • Organizer: 第15回日本再生医療学会総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2016-03-18
• [Presentation] 培養液を用いた未分化ヒトiPS細胞の新規定量測定法（GlycoStem法）の開発 (2016)
  • Author(s): 舘野浩章
  • Organizer: 第２回再生医療産業化展
  • Place of Presentation: インテックス大阪
  • Year and Date: 2016-02-24
  • Invited
• [Presentation] 細胞の品質管理技術の現状と将来 (2016)
  • Author(s): 舘野浩章
  • Organizer: 平成２７年度 先導技術交流会・シンポジウム
  • Place of Presentation: 機械振興会館ホール（地下２階）
  • Year and Date: 2016-01-25
  • Invited
• [Presentation] レクチンを用いた幹細胞評価技術の開発と再生医療への実用化 (2016)
  • Author(s): 舘野浩章
  • Organizer: かがわ糖質バイオフォーラム「複合糖質・糖鎖研究会」
  • Place of Presentation: 香川県立ミュージアム
  • Year and Date: 2016-01-22
  • Invited
• [Presentation] ELIMINATION OF TUMORIGENIC HUMAN PLURIPOTENT STEM CELLS USING A RECOMBINANT LECTIN-TOXIN FUSION PROTEIN (2015)
  • Author(s): 舘野浩章・小沼泰子・伊藤弓弦・平林淳
  • Organizer: 23rd International Symposium on Glycoconjugates
  • Place of Presentation: クロアチア
  • Year and Date: 2015-09-15
  • Int'l Joint Research
• [Presentation] 薬剤融合型レクチンによる腫瘍原生 ヒトiPS/ES細胞除去技術の開発 (2015)
  • Author(s): 舘野浩章・小沼泰子・伊藤弓弦・浅島誠・平林淳
  • Organizer: 平成 27 年度（第 18 回）日本糖質学会
  • Place of Presentation: 東京大学
  • Year and Date: 2015-07-31
• [Presentation] Development and industrial application of lectin-based technologies to detect and eliminate tumorigenic human pluripotent stem cells for safe cell-based therapy (2015)
  • Author(s): 舘野浩章・比江森恵子・鈴木加代・小沼泰子・伊藤弓弦・平林淳
  • Organizer: ISSCR 13th Annual Meeting
  • Place of Presentation: スウェーデン
  • Year and Date: 2015-06-24
  • Int'l Joint Research
• [Presentation] 培養液を用いた非侵襲的造腫瘍性評価技術（GlycoStem法）の開発 (2015)
  • Author(s): 舘野浩章、小沼泰子、伊藤弓弦、福田雅和、藁科雅岐、本多進、浅島誠、平林淳
  • Organizer: 第14回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2015-03-21
• [Presentation] Development of a noninvasive and quantitative detection system of tumorigenic human pluripotent stem cells using cell culture supernatants (2014)
  • Author(s): Hiroaki Tateno, Yasuko Onuma, Yuzuru Ito, Masakazu Fukuda, Masaki Warashina, Susumu Honda, Makoto Asashima, Jun Hirabayashi
  • Organizer: The 5th meeting of Asian Cellular Therapy Organization
  • Place of Presentation: Hyatt Regency Osaka
  • Year and Date: 2014-11-11
• [Presentation] 先端糖鎖プロファイリング技術の開発と再生医療への応用 (2014)
  • Author(s): 舘野浩章
  • Organizer: 第31回医用高分子研究会講座
  • Place of Presentation: 首都大東京秋葉原サテライトキャンパス 秋葉原ダイビル12階1202室
  • Year and Date: 2014-11-10
  • Invited
• [Presentation] 先端糖鎖プロファイリング技術の開発と再生医療への応用 (2014)
  • Author(s): 舘野浩章
  • Organizer: バイオアナリシス2014
  • Place of Presentation: 東北大学薬学部大講義室
  • Year and Date: 2014-11-08
  • Invited
• [Presentation] 未分化細胞特異的レクチンBC2LCNの発見と再生医療への応用 (2014)
  • Author(s): 舘野浩章
  • Organizer: 平成 26 年度（第 17 回）日本糖質学会
  • Place of Presentation: 名古屋大学
  • Year and Date: 2014-08-11
• [Presentation] 糖鎖レクチン工学による幹細胞評価 技術の開発と産業展開 (2014)
  • Author(s): 舘野浩章
  • Organizer: 平成 26 年度（第 17 回）日本糖質学会
  • Place of Presentation: 名古屋大学
  • Year and Date: 2014-08-10
  • Invited
• [Presentation] レクチンを活用した幹細胞評価技術の開発と産業応用 (2014)
  • Author(s): 舘野浩章
  • Organizer: 平成26年度第2回つくばイブニングセミナー
  • Place of Presentation: 産総研つくばセンター本部・情報棟1階ネットワーク会議室
  • Year and Date: 2014-07-25
  • Invited
• [Presentation] 新規未分化細胞特異的プローブ・rBC2LCNの標的分子解明と生細胞イメージングへの応用
  • Author(s): 舘野浩章、小沼泰子、伊藤弓弦、浅島誠、平林淳
  • Organizer: 第32回日本糖質学会
  • Place of Presentation: 大阪国際交流センター
• [Presentation] 高密度レクチンアレイによる新規未分化マーカーrBC2LCNの発見
  • Author(s): 舘野浩章
  • Organizer: BIOtech2013
  • Place of Presentation: 東京ビッグサイト
  • Invited
• [Presentation] DISCOVERY OF A NOVEL PLURIPOTENCY MARKER BC2LCN USING LECTIN MICROARRAY
  • Author(s): 舘野浩章、小沼泰子、伊藤弓弦、浅島誠、平林淳
  • Organizer: ISSCR 11th Annual Meeting
  • Place of Presentation: ボストン
• [Presentation] rBC2LCN, a powerful lectin probe for human pluripotent stem cells
  • Author(s): 小沼泰子、舘野浩章、、平林淳、伊藤弓弦、浅島誠
  • Organizer: ISSCR 11th Annual Meeting
  • Place of Presentation: ボストン
• [Presentation] ポドカリキシンは新規ヒトiPS/ES細胞特異的プローブrBC2LCNの糖タンパク質リガンドである
  • Author(s): 舘野浩章、小沼泰子、伊藤弓弦、浅島誠、平林淳
  • Organizer: 第86回日本生化学会
  • Place of Presentation: パシフィコ横浜
• [Book] バイオチップの基礎と応用 (2015)
  • Author(s): 舘野浩章
  • Total Pages: 274
  • Publisher: シーエムシー出版
• [Book] Topics in Current Chemistry (2015)
  • Author(s): Hirabayashi J, Kuno A, Tateno H
  • Total Pages: 20
  • Publisher: Springer
• [Book] レクチンマイクロアレイによる糖鎖マーカー開発ーがんと多能性幹細胞 (2014)
  • Author(s): 平林淳、舘野浩章、久野敦
  • Total Pages: 6
  • Publisher: メディカルビュー社
• [Book] Sugar Chains (2014)
  • Author(s): Tateno, H. and Hirabayashi, J.
  • Total Pages: 7
  • Publisher: Springer Japan
• [Book] Glycoscience: Biology and Medicine (2014)
  • Author(s): Tateno, H.
  • Total Pages: 12
  • Publisher: Springer Japan
• [Remarks] 移植用細胞から腫瘍を引き起こすヒトiPS/ES細胞を除く技術を開発
  • URL: http://www.aist.go.jp/aist_j/press_release/pr2015/pr20150410/pr20150410.html
• [Remarks] ヒト間葉系幹細胞の分化する能力を評価できる技術を開発
  • URL: http://www.aist.go.jp/aist_j/press_release/pr2016/pr20160404/pr20160404.html
• [Remarks] 再生医療に用いる細胞の安全性を培養液で検査することが可能に
  • URL: http://www.aist.go.jp/aist_j/new_research/nr20140217/nr20140217.html
• [Patent(Industrial Property Rights)] 細胞分化ポテンシャル判別法 (2014)
  • Inventor(s): 舘野浩章、伊藤弓弦、小沼泰子、平林淳
  • Industrial Property Rights Holder: 舘野浩章、伊藤弓弦、小沼泰子、平林淳
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-142919
  • Filing Date: 2014-07-11