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Discovery and Applications of a Novel Human Pluripotent Stem Cell-Specific Lectin Probe rBC2LCN

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Sugar Chains

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Abstract

The cellular glycome of human pluripotent stem cells (hPSCs) such as embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) was exhaustively analyzed using the cutting-edge glycan profiling technology called high-density lectin microarray. Despite the different glycan profiles of the original somatic cells for each tissue, it was found that hiPSCs derived from various origins showed almost the same profile, indicating that the introduction of reprogramming genes caused uniform convergence into glycan structures analogous to those of hESCs. Furthermore, three characteristic features of glycan epitopes expressed in hPSCs were identified: α2-6Sia, α1-2Fuc, and type-1 LacNAc. In addition, a recombinant lectin probe rBC2LCN highly specific to hPSCs was discovered. rBC2LCN is a practical hPSC-specific probe, which enables the live staining of hPSCs just supplemented into cell culture media without visible toxicity. Recently, a noninvasive and quantitative assay of hPSCs with tumorigenic potential using rBC2LCN was also successfully developed. Now rBC2LCN is commercialized as a novel type of detection reagent of hPSCs, which is suitable for industrial application in regenerative medicine. Here, we describe our recent findings about the cellular glycome of hPSCs and the discovery and application of rBC2LCN to regenerative medicine.

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References

  • Andrews PW (2011) Toward safer regenerative medicine. Nat Biotechnol 29:803–805

    Article  CAS  PubMed  Google Scholar 

  • Badcock G, Pigott C, Goepel J, Andrews PW (1999) The human embryonal carcinoma marker antigen TRA-1-60 is a sialylated keratan sulfate proteoglycan. Cancer Res 59:4715–4719

    CAS  PubMed  Google Scholar 

  • Ben-David U, Benvenisty N (2011) The tumorigenicity of human embryonic and induced pluripotent stem cells. Nat Rev Cancer 11:268–277

    Article  CAS  PubMed  Google Scholar 

  • Brennand KJ, Gage FH (2011) Concise review: the promise of human induced pluripotent stem cell-based studies of schizophrenia. Stem Cells 29:1915–1922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Egawa N, Kitaoka S, Tsukita K, Naitoh M, Takahashi K, Yamamoto T, Adachi F, Kondo T, Okita K, Asaka I et al (2012) Drug screening for ALS using patient-specific induced pluripotent stem cells. Sci Transl Med 4:145ra104

    Article  PubMed  Google Scholar 

  • Gagneux P, Varki A (1999) Evolutionary considerations in relating oligosaccharide diversity to biological function. Glycobiology 9:747–755

    Article  CAS  PubMed  Google Scholar 

  • Goldring CE, Duffy PA, Benvenisty N, Andrews PW, Ben-David U, Eakins R, French N, Hanley NA, Kelly L, Kitteringham NR et al (2011) Assessing the safety of stem cell therapeutics. Cell Stem Cell 8:618–628

    Article  CAS  PubMed  Google Scholar 

  • Hasehira K, Tateno H, Onuma Y, Ito Y, Asashima M, Hirabayashi J (2012) Structural and quantitative evidence for dynamic glycome shift on production of induced pluripotent stem cells. Mol Cell Proteomics 11:1913–1923

    Article  PubMed  PubMed Central  Google Scholar 

  • Hentze H, Soong PL, Wang ST, Phillips BW, Putti TC, Dunn NR (2009) Teratoma formation by human embryonic stem cells: evaluation of essential parameters for future safety studies. Stem Cell Res 2:198–210

    Article  PubMed  Google Scholar 

  • Hirabayashi J, Yamada M, Kuno A, Tateno H (2013) Lectin microarrays: concept, principle and applications. Chem Soc Rev 42:4443–4458

    Article  CAS  PubMed  Google Scholar 

  • Imaizumi Y, Okano H (2014) Modeling human neurological disorders with induced pluripotent stem cells. J Neurochem 129(3):388–399

    Google Scholar 

  • Itskovitz-Eldor J (2011) A panel of glycan cell surface markers define pluripotency state and promote safer cell-based therapies. Cell Stem Cell 9:291–292

    Article  CAS  PubMed  Google Scholar 

  • Kamao H, Mandai M, Okamoto S, Sakai N, Suga A, Sugita S, Kiryu J, Takahashi M (2014) Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application. Stem Cell Rep 2:205–218

    Article  CAS  Google Scholar 

  • Kannagi R, Cochran NA, Ishigami F, Hakomori S, Andrews PW, Knowles BB, Solter D (1983) Stage-specific embryonic antigens (SSEA-3 and −4) are epitopes of a unique globo-series ganglioside isolated from human teratocarcinoma cells. EMBO J 2:2355–2361

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kershaw DB, Beck SG, Wharram BL, Wiggins JE, Goyal M, Thomas PE, Wiggins RC (1997) Molecular cloning and characterization of human podocalyxin-like protein. Orthologous relationship to rabbit PCLP1 and rat podocalyxin. J Biol Chem 272:15708–15714

    Article  CAS  PubMed  Google Scholar 

  • Kuno A, Uchiyama N, Koseki-Kuno S, Ebe Y, Takashima S, Yamada M, Hirabayashi J (2005) Evanescent-field fluorescence-assisted lectin microarray: a new strategy for glycan profiling. Nat Methods 2:851–856

    Article  CAS  PubMed  Google Scholar 

  • Kuroda T, Yasuda S, Kusakawa S, Hirata N, Kanda Y, Suzuki K, Takahashi M, Nishikawa S, Kawamata S, Sato Y (2012) Highly sensitive in vitro methods for detection of residual undifferentiated cells in retinal pigment epithelial cells derived from human iPS cells. PLoS One 7:e37342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lanctot PM, Gage FH, Varki AP (2007) The glycans of stem cells. Curr Opin Chem Biol 11:373–380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, Okita K, Mochiduki Y, Takizawa N, Yamanaka S (2008) Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 26:101–106

    Article  CAS  PubMed  Google Scholar 

  • Natunen S, Satomaa T, Pitkanen V, Salo H, Mikkola M, Natunen J, Otonkoski T, Valmu L (2011) The binding specificity of the marker antibodies Tra-1-60 and Tra-1-81 reveals a novel pluripotency-associated type 1 lactosamine epitope. Glycobiology 21:1125–1130

    Article  CAS  PubMed  Google Scholar 

  • Okano H, Nakamura M, Yoshida K, Okada Y, Tsuji O, Nori S, Ikeda E, Yamanaka S, Miura K (2013) Steps toward safe cell therapy using induced pluripotent stem cells. Circ Res 112:523–533

    Article  CAS  PubMed  Google Scholar 

  • Onuma Y, Tateno H, Hirabayashi J, Ito Y, Asashima M (2013) rBC2LCN, a new probe for live cell imaging of human pluripotent stem cells. Biochem Biophys Res Commun 431:524–529

    Article  CAS  PubMed  Google Scholar 

  • Schopperle WM, DeWolf WC (2007) The TRA-1-60 and TRA-1-81 human pluripotent stem cell markers are expressed on podocalyxin in embryonal carcinoma. Stem Cells 25:723–730

    Article  CAS  PubMed  Google Scholar 

  • Schwartz SD, Hubschman JP, Heilwell G, Franco-Cardenas V, Pan CK, Ostrick RM, Mickunas E, Gay R, Klimanskaya I, Lanza R (2012) Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet 379:713–720

    Article  CAS  PubMed  Google Scholar 

  • Strauss S (2010) Geron trial resumes, but standards for stem cell trials remain elusive. Nat Biotechnol 28:989–990

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    Article  CAS  PubMed  Google Scholar 

  • Tang C, Lee AS, Volkmer JP, Sahoo D, Nag D, Mosley AR, Inlay MA, Ardehali R, Chavez SL, Pera RR et al (2011) An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells. Nat Biotechnol 29:829–834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tateno H, Nakamura-Tsuruta S, Hirabayashi J (2007) Frontal affinity chromatography: sugar-protein interactions. Nat Protoc 2:2529–2537

    Article  CAS  PubMed  Google Scholar 

  • Tateno H, Mori A, Uchiyama N, Yabe R, Iwaki J, Shikanai T, Angata T, Narimatsu H, Hirabayashi J (2008) Glycoconjugate microarray based on an evanescent-field fluorescence-assisted detection principle for investigation of glycan-binding proteins. Glycobiology 18:789–798

    Article  CAS  PubMed  Google Scholar 

  • Tateno H, Kuno A, Itakura Y, Hirabayashi J (2010) A versatile technology for cellular glycomics using lectin microarray. Methods Enzymol 478:181–195

    Article  CAS  PubMed  Google Scholar 

  • Tateno H, Toyota M, Saito S, Onuma Y, Ito Y, Hiemori K, Fukumura M, Matsushima A, Nakanishi M, Ohnuma K et al (2011) Glycome diagnosis of human induced pluripotent stem cells using lectin microarray. J Biol Chem 286:20345–20353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tateno H, Matsushima A, Hiemori K, Onuma Y, Ito Y, Hasehira K, Nishimura K, Ohtaka M, Takayasu S, Nakanishi M et al (2013) Podocalyxin is a glycoprotein ligand of the human pluripotent stem cell-specific probe rBC2LCN. Stem Cells Transl Med 2:265–273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tateno H, Onuma Y, Ito Y, Hiemori K, Aiki Y, Shimizu M, Higuchi K, Fukuda M, Warashina M, Honda S et al (2014) A medium hyperglycosylated podocalyxin enables noninvasive and quantitative detection of tumorigenic human pluripotent stem cells. Sci Rep 4:4069

    Article  PubMed  PubMed Central  Google Scholar 

  • Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    Article  CAS  PubMed  Google Scholar 

  • Varki A (1993) Biological roles of oligosaccharides: all of the theories are correct. Glycobiology 3:97–130

    Article  CAS  PubMed  Google Scholar 

  • Yahata N, Asai M, Kitaoka S, Takahashi K, Asaka I, Hioki H, Kaneko T, Maruyama K, Saido TC, Nakahata T et al (2011) Anti-Abeta drug screening platform using human iPS cell-derived neurons for the treatment of Alzheimer’s disease. PLoS One 6:e25788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamanaka S (2009) A fresh look at iPS cells. Cell 137:13–17

    Article  CAS  PubMed  Google Scholar 

  • Yoshida Y, Yamanaka S (2010) Recent stem cell advances: induced pluripotent stem cells for disease modeling and stem cell-based regeneration. Circulation 122:80–87

    Article  PubMed  Google Scholar 

Download references

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Authors and Affiliations

  1. Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 2, 1-1-1 Umezono, Tsukuba, Ibaraki, 305-8568, Japan

    Hiroaki Tateno & Jun Hirabayashi

Authors
  1. Hiroaki Tateno
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  2. Jun Hirabayashi
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Corresponding author

Correspondence to Hiroaki Tateno .

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Editors and Affiliations

  1. Glycometabolome Team, Systems Glycobiology Research Group, RIKEN-Max-Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, Wako, Saitama, Japan

    Tadashi Suzuki

  2. Department of Analytical Biochemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan

    Kazuaki Ohtsubo

  3. Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max-Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, Wako, Saitama, Japan

    Naoyuki Taniguchi

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Tateno, H., Hirabayashi, J. (2015). Discovery and Applications of a Novel Human Pluripotent Stem Cell-Specific Lectin Probe rBC2LCN. In: Suzuki, T., Ohtsubo, K., Taniguchi, N. (eds) Sugar Chains. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55381-6_6

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