Multicellular System Regulation Research Group

Research Project

Glycans cover the outermost layer of all cells and are called “the face of cells” because they change depending on the type and state of cells (differentiation, oncogenesis). We have constructed a recombinant lectin library and have been developing a technology for profiling glycans using lectin library. We have succeeded in developing lectin arrays in which multiple lectins are immobilized on glass slides, and in developing a technology (scGR-seq) for simultaneous analysis of glycan and gene expression in a single cell. We are also working on the development of technologies to measure glycoside hydrolase and glycosyltransferase activities. In addition to the further advancement of their glycan analysis technologies, we are working on the development of diagnostic and therapeutic methods for cancer, brain diseases, metabolic disorders, etc.

Exosomes are nano-sized vesicles covered with a lipid bilayer membrane that are secreted extracellularly from all cells and serve as an important tool for intercellular communication. Furthermore, they are attracting attention as a new bio-material that can be used in the fields of medicine, food, and cosmetics. In collaboration with internal and external experts, we are developing innovative separation technologies for exosomes and tissue-specific designer exosomes using glyco-engineering and chemical labeling technologies. Through this, we aim to apply these technologies to drug delivery and regenerative medicine.

Microwave heating, the well-known example of a microwave oven, is caused by dielectric and conductive losses. This suggests that microwaves have a direct effect on molecules. To elucidate the mechanism of microwave effect on molecules in more detail, we are conducting research on the application of microwaves to the synthesis of multifunctional bioactive substances, fine organic chemistry, biochemistry and other fields. These include 1) development of a system that allows rigid temperature control under microwave irradiation even at low temperatures; 2) practical synthesis of complex glycopeptides by reducing reagent requirements and improving reactivity; 3) application to enzymatic reactions and bio-production; and 4) reduction of energy consumption and use of hazardous substances.

Glycans play essential roles in cell-cell signaling, trafficking, protein folding and so on. Our purpose is to develop synthetic technologies of glycans, glycopeptides, glycolipids and drug candidates to elucidate the mechanisms of biological phenomena related to glycans. We also aim to extend novel glycan analysis technologies to diagnosis and therapy with the synthetic molecules in Project 1 .

Human pluripotent stem cells (hiPSCs) and human mesenchymal stem cells (hMSCs) are expected as cell sources for regenerative medicine. When transplanting these cells into humans, ensuring the safety and quality of the cells is extremely important. So far, we have succeeded in developing a technology for non-destructively detecting and removing the tumorigenic iPSCs remaining in the cells for transplantation and have successfully commercialized it in collaboration with a company. We have also focused on low-quality cells generated in the process of culturing hiPSCs and have been developing technologies for their detection and removal. We will continue to develop new quality control technology of human stem cells.

Aiming to extend healthy life expectancy in an aging society, we will work to construct and elucidate model systems for understanding and evaluating unwellness and disease. As a model to mimic neurological diseases, we will develop a new technology to create human brain organoids that are more similar to living organisms, including glial cells and vasculature, for use as a surrogate animal model and for application to screening methods for drug discovery and functional foods. In addition, we are working to understand the biological basis of social stress and the aging response with social insects, ants, and to search for and develop biomarkers that will contribute to the improvement of unwellness and stress.

Results

• Tateno, H; Mahal, LK; Feizi, T; Kettner, C; Paulson, JC.
  The minimum information required for a glycomics experiment (MIRAGE) project: improving the standards for reporting lectin microarray data.
  GLYCOBIOLOGY. 2025 Feb 19. doi:10.1093/glycob/cwaf006
• Ishii, N; Tateno, H.
  Preparation of Small Extracellular Vesicles Using Sequential Ultrafiltration with Regenerated Cellulose Membranes of Different Molecular Weight Cutoffs: A Study of Morphology and Size by Electron Microscopy.
  MICROSC MICROANAL. 2025 Jan 13. doi:10.1093/mam/ozae133
• Keisham, S; Tateno, H.
  Emerging technologies for single-cell glycomics.
  BBA ADV. 2024 Nov 26. doi:10.1016/j.bbadva.2024.100125
• Hayashi, Y; Tajiri, K; Ozawa, T; Angata, K; Sato, T; Togayachi, A; Nagashima, I; Shimizu, H; Murayama, A; Muraishi, N; Narimatsu, H; Yasuda, I.
  Impact of preS1 Evaluation in the Management of Chronic Hepatitis B Virus Infection.
  MEDICINA (Kaunas). 2024 Aug 16;60(8):1334. doi: 10.3390/medicina60081334
• Satoh, T; Yagi-Utsumi, M; Ishii, N; Mizushima, T; Yagi, H; Kato, R; Tateno, H; Matsuo, I; Kato, K; Suzuki, T; Yoshida, Y.
  Structural basis of sugar recognition by SCFFBS2 ubiquitin ligase involved in NGLY1 deficiency.
  FEBS LETTERS. 2024 Aug 22. doi: 10.1002/1873-3468.15003
• Páez-Watson, T; Tomás-Martínez, S; de, Wit R; Keisham, S; Tateno, H; van, Loosdrecht MCM; Lin, Y.
  Sweet Secrets: Exploring Novel Glycans and Glycoconjugates in the Extracellular Polymeric Substances of “Candidatus Accumulibacter”.
  ACS ES T WATER. 2024 Jul 12;4(8):3391-3399. doi: 10.1021/acsestwater.4c00247
• Yamasaki, K; Tsuzuki, S; Tateno, H.
  Stabilization of the Protein Structure by the Many-Body Cooperative Effect in the NH/π Hydrogen-bonding Tryptophan Triad.
  J PHYS CHEM B. 2024 Jul 17. doi: 10.1021/acs.jpcb.4c02391
• Arai, J; Hayakawa, Y; Tateno, H; Fujiwara, H; Kasuga, M; Fujishiro, M.
  The role of gastric mucins and mucin-related glycans in gastric cancers.
  CANCER SCI. 2024 Jul 19. doi: 10.1111/cas.16282
• Wang, ZG; Yang, ZH; Shishido, M; Daoudi, K; Hidaka, M; Tateno, H; Futai, E; Ogawa, T.
  Microcystis viridis NIES-102 Cyanobacteria Lectin (MVL) Interacts with SARS-CoV-2 Spike Protein Receptor Binding Domains (RBDs) via Protein-Protein Interaction.
  INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2024 Jun 18;25(12):6696. doi: 10.3390/ijms25126696
• Nie, H; Saini, P; Miyamoto, T; Liao, L; Zielinski, RJ; Liu, H; Zhou, W; Wang, C; Murphy, B; Towers, M; Yang, T; Qi, Y; Kannan, T; Kossenkov, A; Tateno, H; Claiborne, DT; Zhang, N; Abdel-Mohsen, M; Zhang, R.
  Targeting branched N-glycans and fucosylation sensitizes ovarian tumors to immune checkpoint blockade.
  NAT COMMUN. 2024 Apr 2;15(1):2853. doi: 10.1038/s41467-024-47069-y
• Arai, J; Hayakawa, Y; Tateno, H; Murakami, K; Hayashi, T; Hata, M; Matsushita, Y; Kinoshita, H; Abe, S; Kurokawa, K; Oya, Y; Tsuboi, M; Ihara, S; Niikura, R; Suzuki, N; Iwata, Y; Shiokawa, T; Shiomi, C; Uekura, C; Yamamoto, K; Fujiwara, H; Kawamura, S; Nakagawa, H; Mizuno, S; Kudo, T; Takahashi, S; Ushiku, T; Hirata, Y; Fujii, C; Nakayama, J; Shibata, S; Woods, S; Worthley, DL; Hatakeyama, M; Wang, TC; Fujishiro, M.
  Impaired glycosylation of gastric mucins drives gastric tumorigenesis and serves as a novel therapeutic target.
  GASTROENTEROLOGY. 2024 Apr 5:S0016-5085(24)00363-9. doi: 10.1053/j.gastro.2024.03.037
• Nakahashi, H; Oda, T; Shimomura, O; Akashi, Y; Takahashi, K; Miyazaki, Y; Furuta, T; Kuroda, Y; Louphrasitthiphol, P; Mathis, BJ; Tateno, H.
  Aberrant Glycosylation in Pancreatic Ductal Adenocarcinoma 3D Organoids Is Mediated by KRAS Mutations.
  J ONCOL. 2024 Mar 18;2024:1529449. doi: 10.1155/2024/1529449
• Nagashima, I; Shimizu, H.
  Preparation of Mucin Glycopeptides by Organic Synthesis.
  METHODS MOL BIOL. 2024;2763:187-199. doi: 10.1007/978-1-0716-3670-1_16
• Chen, LM; Keisham, S; Tateno, H; van, Ede J; Pronk, M; van, Loosdrecht MCM; Lin, Y.
  Alterations of Glycan Composition in Aerobic Granular Sludge during the Adaptation to Seawater Conditions.
  ACS ES T WATER. 2023 Dec 27;4(1):279-286. doi: 10.1021/acsestwater.3c00625
• Keisham, S; Saito, S; Kowashi, S; Tateno, H.
  Droplet-Based Glycan and RNA Sequencing for Profiling the Distinct Cellular Glyco-States in Single Cells.
  SMALL METHODS. 2024 Jan 2:e2301338. doi: 10.1002/smtd.202301338
• Yonezawa, A; Mizushima, K; Hirai, Y; Tateno, H; Muto, A; Igarashi, K; Takag, T; Naito, Y; Higashimura, Y.
  Involvement of transcription repressor Bach1 in function of intestinal goblet cells.
  ANNALS OF NUTRITION AND METABOLISM. 2023;79 (suppl 1) 1170-1170; AUG. doi: 10.1159/000530786
• Odaka, H.
  Target-Specific O-linked N-acetylglucosamine Modification with a Dual-Specificity Aptamer Reveals Functions of O-GlcNAcylation in beta-catenin.
  TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY. May 25, 2023; Volume 35(2023) Issue 205. doi: 10.4052/tigg.2309.6E
• Watanabe, T, Tateno, H.
  Lectin Blotting of Cell Lysates.
  CURR PROTOC. 2023 May;3(5):e790. doi: 10.1002/cpz1.790
• Kuroda, Y; Oda, T; Shimomura, O; Louphrasitthiphol, P; Mathis, BJ; Tateno, H, Hatano, K.
  Novel positron emission tomography imaging targeting cell surface glycans for pancreatic cancer: (18) F-labeled rBC2LCN lectin.
  CANCER SCI. 2023 May 19. doi: 10.1111/cas.15846
• Odaka, H; Tateno, H.
  Single-Cell Glycan and RNA Sequencing (scGR-seq).
  CURR PROTOC. 2023 May;3(5):e777. doi: 10.1002/cpz1.777
• Sato, Y; Kato, Y; Iizumi, Y; Morimoto, T; Kobashi, K; Sugino, T; Tateno, H; Okazaki, T.
  Size distributions of cellulose nanocrystals in dispersions using the centrifugal sedimentation method.
  INT J BIOL MACROMOL. 2023 Feb 2:123520. doi: 10.1016/j.ijbiomac.2023.123520
• Mawaribuchi, S; Shimomura, O; Oda, T; Hiemori, K; Shimizu, K; Yamase, K; Date, M; Tateno, H.
  rBC2LCN-reactive SERPINA3 is a glycobiomarker candidate for pancreatic ductal adenocarcinoma.
  GLYCOBIOLOGY. 2023 Feb 2:cwad009. doi: 10.1093/glycob/cwad009
• Huang, T; Sato, Y; Kuramochi, A; Ohba, Y; Sano, M; Miyagishi, M; Tateno, H; Wadhwa, R; Kawasaki, K; Uchida, T; Ekdahl, KN; Nilsson, B; Chung, UI; Teramura, Y.
  Surface modulation of extracellular vesicles with cell-penetrating peptide-conjugated lipids for improvement of intracellular delivery to endothelial cells.
  REGEN THER. 2023 Jan 11;22:90-98. doi: 10.1016/j.reth.2022.12.007
• Nagashima, I; Sugiyama, JI; Shimizu, H.
  Study of 400 MHz microwave conduction loss effect for a hydrolysis reaction by thermostable β-Glucosidase HT1.
  BIOSCI BIOTECHNOL BIOCHEM. 2022 Dec 6:zbac194. doi: 10.1093/bbb/zbac194
• Kuroda, Y; Shimomura, O; Nakahashi, H; Miyazaki, Y; Nakajima, T; Tateno, H; Oda, T.
  Lectin-based photoimmunotherapy targeting cell surface glycans for pancreatic cancer.
  CANCER RESEARCH 82 (22). 2022 NOV 15. doi: 10.1158/1538-7445.PANCA22-B083
• Kuroda, Y; Oda, T; Shimomura, O; Hashimoto, S; Akashi, Y; Miyazaki, Y; Furuya, K; Furuta, T; Nakahashi, H; Louphrasitthiphol, P; Mathis, BJ; Nakajima,T; Tateno, H.
  Lectin-based phototherapy targeting cell surface glycans for pancreatic cancer.
  INT J CANCER. 2022 Nov 22. doi: 10.1002/ijc.34362
• Tasaki, M; Tateno, H; Sato, T; Narimatsu, H; Saito, K; Nakagawa, Y; Aoki, T; Kamimura, M; Ushiki, T; Takahashi, K; Tomita, Y.
  Hyporesponsiveness against donors ABO antigens of renal grafts after ABO-incompatible kidney transplantation.
  CLIN EXP NEPHROL. 2022 Oct 8. doi: 10.1007/s10157-022-02280-3
• Kosaka, T; Yamaguchi, S; Izuta, S; Yamahira, S; Shibasaki, Y; Tateno, H; Okamoto, A.
  Bioorthogonal Photoreactive Surfaces for Single-Cell Analysis of Intercellular Communications.
  AM CHEM SOC. 2022 Sep 20. doi: 10.1021/jacs.2c07321
• Yamasaki, K; Adachi, N; Ngwe Tun, MM; Ikeda, A; Moriya, T; Kawasaki, M; Yamasaki, T; Kubota, T; Nagashima, I; Shimizu, H; Tateno, H; Morita, K.
  Core fucose-specific Pholiota squarrosa lectin (PhoSL) as a potent broad-spectrum inhibitor of SARS-CoV-2 infection.
  FEBS J. 2022 Aug 25. doi: 10.1111/febs.16599
• Numakawa, T; Odaka, H.
  The Role of Neurotrophin Signaling in Age-Related Cognitive Decline and Cognitive Diseases.
  INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2022 Jul 13;23(14):7726. doi: 10.3390/ijms23147726
• Kokubu, R; Ohno, S; Kuratani, H; Takahashi, Y; Manabe, N; Shimizu, H; Chiba, Y; Denda-Nagai, K; Tsuiji, M; Irimura, T; Yamaguchi, Y.
  O-Glycan-Dependent Interaction between MUC1 Glycopeptide and MY.1E12 Antibody by NMR, Molecular Dynamics and Docking Simulations.
  INT J MOL SCI. 2022 Jul 16;23(14):7855. doi: 10.3390/ijms23147855
• Nagae, M; Hirata, T; Tateno, H; Mishra, SK; Manabe, N; Osada, N; Tokoro, Y; Yamaguchi, Y; Doerksen, RJ; Shimizu, T; Kizuka, Y.
  Discovery of a lectin domain that regulates enzyme activity in mouse N-acetylglucosaminyltransferase-IVa (MGAT4A).
  COMMUN BIOL. 2022 Jul 19;5(1):695. doi: 10.1038/s42003-022-03661-w
• Odaka, H.
  Genome-wide CRISPR/Cas9 Screening Identifies KDM2B as a Modifier of Heparan Sulfate-Protein Interactions.
  TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY. 2022 Volume 34 Issue 199 Pages E63. doi: 10.4052/tigg.2203.6E
• Tsukano, K; Yamamoto, T; Watanabe, T; Michiue, T.
  Xenopus Dusp6 modulates FGF signaling to precisely pattern pre-placodal ectoderm.
  DEVELOPMENTAL BIOLOGY. 2022 May 16. doi: 10.1016/j.ydbio.2022.05.009
• Oinam, L; Tateno, H.
  Glycan Profiling by Sequencing to Uncover Multicellular Communication: Launching Glycobiology in Single Cells and Microbiomes.
  FRONT CELL DEV BIOL. 2022 May 27;10:919168. doi: 10.3389/fcell.2022.919168
• Yang, Y; Akashi, Y; Shimomura, O; Tateno, H; Saito, S; Hiemori, K; Miyazaki, Y; Furuta, T; Kitaguchi, D; Kuroda, Y; Pakavarin, L; Oda, T.
  Glycan expression profile of signet ring cell gastric cancer cells and potential applicability of rBC2LCN-targeted lectin drug conjugate therapy.
  GASTRIC CANCER. 2022 Jun 17. doi: 10.1007/s10120-022-01312-x
• Odaka, H; Hiemori, K; Shimoda, A; Akiyoshi, K; Tateno, H.
  CD63-positive extracellular vesicles are potential diagnostic biomarkers of pancreatic ductal adenocarcinoma.
  BMC GASTROENTEROLOGY. 2022 Mar 28;22(1):153. doi: 10.1186/s12876-022-02228-7
• Hayashi, Y; Yimiti, D; Sanada, Y; Ding, C; Omoto, T; Ogura, T; Nakasa, T; Ishikawa, M; Hiemori, K; Tateno, H; Miyaki, S; Adachi, N.
  The therapeutic capacity of bone marrow MSC-derived extracellular vesicles in Achilles tendon healing is passage-dependent and indicated by specific glycans.
  FEBS LETTERS. 2022 Apr;596(8):1047-1058. doi: 10.1002/1873-3468.14333
• Tasaki, M; Tateno, H; Sato, T; Tomioka, A; Kaji, H; Narimatsu, H; Saito, K; Nakagawa, Y; Aoki, T; Kamimura, M; Ushiki, T; Okada, M; Miwa, Y; Hotta, K; Yoshida, Y; Takahashi, K; Tomita, Y.
  A Novel Method of CD31-Combined ABO Carbohydrate Antigen Microarray Predicts Acute Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation.
  TRANSPL INT. 2022 Mar 23;35:10248. doi: 10.3389/ti.2022.10248
• Oinam, L; Hayashi, R; Hiemori, K; Kiyoi, K; Sage-Ono, K; Miura, K; Ono, M; Tateno, H.
  Quantitative evaluation of glycan-binding specificity of recombinant Concanavalin A produced in lettuce (Lactuca sativa).
  BIOTECHNOL BIOENG. 2022 Apr 8. doi: 10.1002/bit.28099
• Seo, N; Nakamura, J; Kaneda, T; Tateno, H; Shimoda, A; Ichiki, T; Furukawa, K; Hirabayashi, J; Akiyoshi, K; Shiku, H.
  Distinguishing functional exosomes and other extracellular vesicles as a nucleic acid cargo by the anion-exchange method.
  J EXTRACELL VESICLES. 2022 Mar;11(3):e12205. doi: 10.1002/jev2.12205
• Odaka, H; Ozaki, H; Tateno, H.
  scGR-seq: Integrated analysis of glycan and RNA in single cells.
  STAR PROTOC. 2022 Feb 18;3(1):101179. doi: 10.1016/j.xpro.2022.101179. eCollection
• Irumagawa, S; Hiemori, K; Saito, S; Tateno, H; Arai, R.
  Self-Assembling Lectin Nano-Block Oligomers Enhance Binding Avidity to Glycans.
  INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 23 (2);doi: 10.3390/ijms23020676 JAN
• Oinam, L; Tateno, H.
  Evaluation of Glycan-Binding Specificity by Glycoconjugate Microarray with an Evanescent-Field Fluorescence Detection System.
  METHODS MOL BIOL. 2022;2460:25-32. doi: 10.1007/978-1-0716-2148-6_2
• Kaifu, T; Yabe, R; Maruhashi, T; Chung, SH; Tateno, H; Fujikado, N; Hirabayashi, J; Iwakura, Y.
  DCIR and its ligand asialo-biantennary N-glycan regulate DC function and osteoclastogenesis.
  J EXP MED. 2021 Dec 6;218(12):e20210435. doi: 10.1084/jem.20210435. Epub 2021 Nov
• Shimoda, A; Miura, R; Tateno, H; Seo, N; Shiku, H; Sawada, S; Sasaki, Y; Akiyoshi, K.
  Assessment of Surface Glycan Diversity on Extracellular Vesicles by Lectin Microarray and Glycoengineering Strategies for Drug Delivery Applications.
  SMALL METHODS; doi: 10.1002/smtd.202100785
• Tulin, EKC; Nakazawa, C; Nakamura, T; Saito, S; Ohzono, N; Hiemori, K; Nakakita, SI; Tateno, H; Tonozuka, T; Nishikawa, A.
  Glycan detecting tools developed from the Clostridium botulinum whole hemagglutinin complex.
  SCI REP. 2021 Nov 9;11(1):21973. doi: 10.1038/s41598-021-01501-1
• Kaigawa, H; Tateno, H; Arai, R.
  Self-Assembling Functional Complexes of Protein Nanobuilding Blocks with a Trimeric Lectin.
  PROTEIN SCIENCE 30 158-159; OCT
• Irumagawa, S; Tateno, H; Arai, R.
  Self-Assembling Lectin Nano-Building Blocks Enhance Avidity to Glycans through Polyvalent Effect.
  PROTEIN SCIENCE 30 173-174; OCT
• Hoshi, K; Ito, H; Abe, E; Fuwa, TJ; Kanno, M; Murakami, Y; Abe, M; Murakami, T, Yoshihara, A, Ugawa, Y, Saito, T, Saido, TC, Matsumoto, K, Yamaguchi, Y, Furukawa, K, Arai, H, Kanai, M, Miyajima, M, Arai, H, Ogawa, N, Akatsu, H, Hashizume, Y, Tateno, H, Honda, T, Hashimoto, Y.
  Transferrin Biosynthesized in the Brain Is a Novel Biomarker for Alzheimers Disease.
  METABOLITES. 2021 Sep 10;11(9):616. doi: 10.3390/metabo11090616
• Angata, K; Wagatsuma, T; Togayachi, A; Sato, T; Sogabe, M; Tajiri, K; Ozawa, T; Nagashima, I; Shimizu, H; Iijima, S; Korenaga, M; Kuno, A; Kaji, H; Mizokami, M; Narimatsu, H.
  O-glycosylated HBsAg peptide can induce specific antibody neutralizing HBV infection.
  BIOCHIM BIOPHYS ACTA GEN SUBJ. 2021 Sep 25:130020. doi: 10.1016/j.bbagen.2021.130020
• Minoshima, F; Ozaki, H; Odaka, H; Tateno, H.
  Integrated analysis of glycan and RNA in single cells.
  ISCIENCE. 2021 Jul 17;24(8):102882. doi: 10.1016/j.isci.2021.102882. eCollection
• Watanabe, T; Takeda, K; Hiemori, K; Minamisawa, T; Tateno, H.
  A glycosaminoglycan microarray identifies the binding of SARS-CoV-2 spike protein to chondroitin sulfate E.
  FEBS LETT. 2021 Aug 10. doi: 10.1002/1873-3468.14173
• Furuta, T; Oda, T; Kiyoi, K; Ozawa, Y; Kimura, S; Kurimori, K; Miyazaki, Y; Yu, Y; Furuya, K; Akashi, Y; Shimomura, O; Tateno, H
  Carcinoembryonic antigen as a specific glycoprotein ligand of rBC2LCN lectin on pancreatic ductal adenocarcinoma cells
  Cancer Sci. 2021 Jun 11. doi: 10.1111/cas.15023
• Numakawa, T; Odaka, H.
  Brain-Derived Neurotrophic Factor Signaling in the Pathophysiology of Alzheimers Disease: Beneficial Effects of Flavonoids for Neuroprotection.
  INT J MOL SCI. 2021 May 27;22(11):5719. doi: 10.3390/ijms22115719
• Watanabe, T; Tateno, H.
  Elimination of cells deviated from human induced pluripotent stem cells with a photoactivatable IR700-labelled antibody.
  BIOCHEM BIOPHYS RES COMMUN. 2021 Mar 25;554:13-18. doi: 10.1016/j.bbrc.2021.03.078