A large variety of glycans is intricately located on the cell surface, and the overall profile (the glycome, given the entire repertoire of glycoconjugate-associated sugars in cells and tissues) is believed to be crucial for the diverse roles of glycans, which are mediated by specific interactions that control cell-cell adhesion, immune response, microbial pathogenesis and other cellular events. The glycomic profile also reflects cellular alterations, such as development, differentiation and cancerous change. A glycoconjugate-based approach would therefore be expected to streamline discovery of novel cellular biomarkers. Development of such an approach has proven challenging, due to the technical difficulties associated with the analysis of various types of cellular glycomes; however, recent progress in the development of analytical methodologies and strategies has begun to clarify the cellular glycomics of various classes of glycoconjugates. This review focuses on recent advances in the technical aspects of cellular glycomic analyses of major classes of glycoconjugates, including N- and O-linked glycans, derived from glycoproteins, proteoglycans and glycosphingolipids. Articles that unveil the glycomics of various biologically important cells, including embryonic and somatic stem cells, induced pluripotent stem (iPS) cells and cancer cells, are discussed.
Takahashi, K.; Tanabe, K.; Ohnuki, M.; Narita, M.; Ichisaka, T.; Tomoda, K.; Yamanaka, S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007, 131, 861–872, doi:10.1016/j.cell.2007.11.019.
[3]
Karsdal, M.A.; Henriksen, K.; Leeming, D.J.; Mitchell, P.; Duffin, K.; Barascuk, N.; Klickstein, L.; Aggarwal, P.; Nemirovskiy, O.; Byrjalsen, I.; et al. Biochemical markers and the FDA Critical Path: how biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development. Biomarkers 2009, 14, 181–202, doi:10.1080/13547500902777608.
[4]
Bertolini, F.; Mancuso, P.; Shaked, Y.; Kerbel, RS. Molecular and cellular biomarkers for angiogenesis in clinical oncology. Drug Discovery Today 2007, 12, 806–812, doi:10.1016/j.drudis.2007.08.011.
[5]
Kannagi, R.; Cochran, N.A.; Ishigami, F.; Hakomori, S.; Andrews, P.W.; Knowles, B.B.; Solter, D. Stage-specific embryonic antigens (SSEA-3 and -4) are epitopes of a unique globo-series ganglioside isolated from human teratocarcinoma cells. EMBO J. 1983, 2, 2355–2361.
[6]
Lee, J.B.; Kim, J.M.; Kim, S.J.; Park, J.H.; Hong, S.H.; Roh, S.I.; Kim, M.K.; Yoon, H.S. Comparative characteristics of three human embryonic stem cell lines. Mol. Cells 2005, 19, 31–38.
[7]
Natunen, S.; Satomaa, T.; Pitk？nen, V.; Salo, H.; Mikkola, M.; Natunen, J.; Otonkoski, T.; Valmu, L. The binding specificity of the marker antibodies Tra-1-60 and Tra-1-81 reveals a novel pluripotency-associated type 1 lactosamine epitope. Glycobiology 2011, 21, 1125–1130.
[8]
Lanctot, P.M.; Gage, F.H.; Varki, A.P. The glycans of stem cells. Curr. Opin. Chem. Biol. 2007, 11, 373–380, doi:10.1016/j.cbpa.2007.05.032.
[9]
Angata, T.; Fujinawa, R.; Kurimoto, A.; Nakajima, K.; Kato, M.; Takamatsu, S.; Korekane, H.; Gao, C.X.; Ohtsubo, K.; Kitazume, S.; Taniguchi, N. Integrated approach toward the discovery of glyco-biomarkers of inflammation-related diseases. Ann. N. Y. Acad. Sci. 2012, 1253, 159–169.
[10]
Ludwig, J.A.; Weinstein, J.N. Biomarkers in cancer staging; prognosis and treatment selection. Nat. Rev. Cancer 2005, 5, 845–856, doi:10.1038/nrc1739.
[11]
Rillahan, C.D.; Paulson, J.C. Glycan microarrays for decoding the glycome. Annu. Rev. Biochem. 2011, 80, 797–823, doi:10.1146/annurev-biochem-061809-152236.
[12]
Freeze, H.H. Genetic defects in the human glycome. Nat. Rev. Genet. 2006, 7, 537–551, doi:10.1038/nrg1894.
[13]
Gabius, H.J.; André, S.; Jiménez-Barbero, J.; Romero, A.; Solís, D. From lectin structure to functional glycomics: principles of the sugar code. Trends Biochem. Sci. 2011, 36, 298–313, doi:10.1016/j.tibs.2011.01.005.
[14]
Stanley, P.; Cummings, R.D. Structures Common to Different Glycans. In Essentials of Glycobiology, 2nd; Varki, A., Cummings, R.D., Esko, J.D., Freeze, H.H., Stanley, P., Bertozzi, C.R., Hart, G.W., Etzler, M.E., Eds.; Cold Spring Harbor Laboratory Press: New York, NY, USA, 2009; pp. 175–198.
[15]
Furukawa, K.; Takamiya, K.; Okada, M.; Inoue, M.; Fukumoto, S.; Furukawa, K. Novel function of complex carbohydrates elucidated by the mutant mice of glycosyltransferase genes. Biochim. Biophys. Acta 2001, 1525, 1–12, doi:10.1016/S0304-4165(00)00185-9.
[16]
Helenius, A.; Aebi, M. Intracellular functions of N-linked glycans. Science 2001, 291, 2364–2369, doi:10.1126/science.291.5512.2364.
[17]
Hebert, D.N.; Molinari, M. Flagging and docking: dual roles for N-glycans in protein quality control and cellular proteostasis. Trends Biochem Sci. 2012, 37, 404–410, doi:10.1016/j.tibs.2012.07.005.
[18]
Wada, Y.; Azadi, P.; Costello, C.E.; Dell, A.; Dwek, R.A.; Geyer, R.; Kakehi, K.; Karisson, N.G.; Kato, K.; Kawasaki, N.; et al. Comparison of the methods for profiling glycoprotein glycans--HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. Glycobiology 2007, 17, 411–422, doi:10.1093/glycob/cwl086.
[19]
Naven, T.J.; Harvey, D.J. Effect of structure on the signal strength of oligosaccharides in matrix-assisted laser desorption/ionization mass spectrometry on time-of-flight and magnetic sector instruments. Rapid Commun. Mass Spectrom. 1996, 10, 1361–1366, doi:10.1002/(SICI)1097-0231(199608)10:11<1361::AID-RCM642>3.0.CO;2-A.
[20]
Powell, A.K.; Harvey, D.J. Stabilization of sialic acids in N-linked oligosaccharides and gangliosides for analysis by positive ion matrix-assisted laser desorption/ionization mass spectrometry. Rapid Commun. Mass Spectrom. 1996, 10, 1027–1032, doi:10.1002/(SICI)1097-0231(19960715)10:9<1027::AID-RCM634>3.0.CO;2-Y.
[21]
Miura, Y.; Shinohara, Y.; Furukawa, J.; Nagahori, N.; Nishimura, S. Rapid and simple solid-phase esterification of sialic acid residues for quantitative glycomics by mass spectrometry. Chem. Eur. J. 2007, 13, 4797–4804, doi:10.1002/chem.200601872.
[22]
Dell, A.; Morris, H.R. Glycoprotein structure determination by mass spectrometry. Science 2001, 291, 2351–2356, doi:10.1126/science.1058890.
[23]
Kita, Y.; Miura, Y.; Furukawa, J.; Nakano, M.; Shinohara, Y.; Ohno, M.; Takimoto, A.; Nishimura, S. Quantitative glycomics of human whole serum glycoproteins based on the standardized protocol for liberating N-glycans. Mol. Cell Proteomics 2007, 6, 1437–1445, doi:10.1074/mcp.T600063-MCP200.
[24]
Krishnamoorthy, L.; Mahal, L.K. Glycomic analysis: an array of technologies. ACS Chem. Biol. 2009, 4, 715–732, doi:10.1021/cb900103n.
[25]
Ruhaak, L.R.; Zauner, G.; Huhn, C.; Bruggink, C.; Deelder, A.M.; Wuhrer, M. Glycan labeling strategies and their use in identification and quantification. Anal. Bioanal. Chem. 2010, 397, 3457–3481, doi:10.1007/s00216-010-3532-z.
Jeong, H.J.; Kim, Y.G.; Yang, Y.H.; Kim, B.G. High-throughput quantitative analysis of total N-glycans by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Anal. Chem. 2012, 84, 3453–3460, doi:10.1021/ac203440c.
[28]
Lemoine, J.; Chirat, F.; Domon, B. Structural analysis of derivatized oligosaccharides using post-source decay matrix-assisted laser desorption/ionization mass spectrometry. J. Mass Spectrom. 1996, 31, 908–912, doi:10.1002/(SICI)1096-9888(199608)31:8<908::AID-JMS376>3.0.CO;2-D.
[29]
North, S.J.; Huang, H.H.; Sundaram, S.; Jang-Lee, J.; Etienne, A.T.; Trollope, A.; Chalabi, S.; Dell, A.; Stanley, P.; Haslam, S.M. Glycomics profiling of Chinese hamster ovary cell glycosylation mutants reveals N-glycans of a novel size and complexity. J. Biol Chem. 2010, 285, 5759–5775.
[30]
Antonopoulos, A.; North, S.J.; Haslam, S.M.; Dell, A. Glycosylation of mouse and human immune cells: insights emerging from N-glycomics analyses. Biochem. Soc. Trans. 2011, 39, 1334–1340, doi:10.1042/BST0391334.
[31]
Satomaa, T.; Heiskanen, A.; Mikkola, M.; Olsson, C.; Blomqvist, M.; Tiittanen, M.; Jaatinen, T.; Aitio, O.; Olonen, A.; Helin, J.; et al. The N-glycome of human embryonic stem cells. BMC Cell Biol. 2009, 10, 42, doi:10.1186/1471-2121-10-42.
[32]
Furukawa, J.; Shinohara, Y.; Kuramoto, H.; Miura, Y.; Shimaoka, H.; Kurogochi, M.; Nakano, M.; Nishimura, S. Comprehensive approach to structural and functional glycomics based on chemoselective glycoblotting and sequential tag conversion. Anal. Chem. 2008, 80, 1094–1101.
[33]
Uematsu, R.; Furukawa, J.; Nakagawa, H.; Shinohara, Y.; Deguchi, K.; Monde, K.; Nishimura, S. High throughput quantitative glycomics and glycoform-focused proteomics of murine dermis and epidermis. Mol. Cell. Proteomics 2005, 4, 1977–1989.
[34]
Uematsu, R.; Shinohara, Y.; Nakagawa, H.; Kurogochi, M.; Furukawa, J.; Miura, Y.; Akiyama, M.; Shimizu, H.; Nishimura, S. Glycosylation specific for adhesion molecules in epidermis and its receptor revealed by glycoform-focused reverse genomics. Mol. Cell. Proteomics 2009, 8, 232–244.
[35]
Amano, M.; Yamaguchi, M.; Takegawa, Y.; Yamashita, T.; Terashima, M.; Furukawa, J.; Miura, Y.; Shinohara, Y.; Iwasaki, N.; Minami, A.; Nishimura, S. Threshold in stage-specific embryonic glycotypes uncovered by a full portrait of dynamic N-glycan expression during cell differentiation. Mol. Cell Proteomics 2010, 9, 523–537, doi:10.1074/mcp.M900559-MCP200.
[36]
Hase, S.; Hara, S.; Matsushima, Y. Tagging of sugars with a fluorescent compound, 2-aminopyridine. J. Biochem. 1979, 85, 217–220.
[37]
Bigge, J.C.; Patel, T.P.; Bruce, J.A.; Goulding, P.N.; Charles, S.M.; Parekh, R.B. Nonselective and efficient fluorescent labeling of glycans using 2-amino benzamide and anthranilic acid. Anal. Biochem. 1995, 230, 229–238.
[38]
Wuhrer, M.; de Boer, A.R.; Deelder, A.M. Structural glycomics using hydrophilic interaction chromatography (HILIC) with mass spectrometry. Mass Spectrom Rev. 2009, 28, 192–206, doi:10.1002/mas.20195.
[39]
Takegawa, Y.; Deguchi, K.; Keira, T.; Ito, H.; Nakagawa, H.; Nishimura, S. Separation of isomeric 2-aminopyridine derivatized N-glycans and N-glycopeptides of human serum immunoglobulin G by using a zwitterionic type of hydrophilic-interaction chromatography. J. Chromatogr. A 2006, 1113, 177–181, doi:10.1016/j.chroma.2006.02.010.
[40]
Packer, N.H.; Lawson, M.A.; Jardine, D.R.; Redmond, J.W. A general approach to desalting oligosaccharides released from glycoproteins. Glycoconj. J. 1998, 15, 737–747, doi:10.1023/A:1006983125913.
[41]
Zaia, J. Mass spectrometry and glycomics. OMICS 2010, 14, 401–418, doi:10.1089/omi.2009.0146.
[42]
An, H.J.; Gip, P.; Kim, J.; Wu, S.; Park, K.W.; McVaugh, C.T.; Schaffer, D.V.; Bertozzi, C.R.; Lebrilla, C.B. Extensive determination of glycan heterogeneity reveals an unusual abundance of high mannose glycans in enriched plasma membranes of human embryonic stem cells. Mol. Cell Proteomics 2012, 11, M111.010660, doi:10.1074/mcp.M111.010660.
[43]
Hasehira, K.; Tateno, H.; Onuma, Y.; Ito, Y.; Asashima, M.; Hirabayashi, J. Structural and quantitative evidence for dynamic glycome shift upon production of human induced pluripotent stem cells. Mol. Cell Proteomics 2012, 11, 1913–1923, doi:10.1074/mcp.M112.020586.
[44]
Zhang, H.; Li, X.J.; Martin, D.B.; Aebersold, R. Entification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nat. Biotech. 2003, 21, 660–666.
[45]
Baycin-Hizal, D.; Tabb, D.L.; Chaerkady, R.; Chen, L.; Lewis, N.E.; Nagarajan, H.; Sarkaria, V.; Kumar, A.; Wolozny, D.; Colao, J.; et al. Proteomic analysis of chinese hamster ovary cells. J. Proteome. Res. 2012, 11, 5265–5276.
[46]
Sudhir, P.R.; Chen, C.H.; Pavana Kumari, M.; Wang, M.J.; Tsou, C.C.; Sung, T.Y.; Chen, J.Y.; Chen, C.H. Label-free quantitative proteomics and N-glycoproteomics analysis of KRAS-activated human bronchial epithelial cells. Mol. Cell Proteomics 2012, 11, 901–915, doi:10.1074/mcp.M112.020875.
[47]
Almaraz, R.T.; Tian, Y.; Bhattarcharya, R.; Tan, E.; Chen, S.H.; Dallas, M.R.; Chen, L.; Zhang, Z.; Zhang, H.; Konstantopoulos, K.; et al. Metabolic flux increases glycoprotein sialylation: implications for cell adhesion and cancer metastasis. Mol. Cell Proteomics 2012, 11, M112.017558.
[48]
Kurogochi, M.; Matsushista, T.; Amano, M.; Furukawa, J.; Shinohara, Y.; Aoshima, M.; Nishimura, S. Sialic acid-focused quantitative mouse serum glycoproteomics by multiple reaction monitoring assay. Mol. Cell. Proteomics 2010, 9, 2354–2368, doi:10.1074/mcp.M110.000430.
[49]
Zhang, Y.; Yin, H.; Lu, H. Recent progress in quantitative glycoproteomics. Glycoconj. J. 2012, 29, 249–258, doi:10.1007/s10719-012-9398-x.
[50]
Li, Y.; Tian, Y.; Rezai, T.; Prakash, A.; Lopez, M.F.; Chan, D.W.; Zhang, H. Simultaneous analysis of glycosylated and sialylated prostate-specific antigen revealing differential distribution of glycosylated prostate-specific antigen isoforms in prostate cancer tissues. Anal. Chem. 2011, 83, 240–245.
[51]
Jensen, O.N. Interpreting the protein language using proteomics. Nat. Rev. Mol. Cell. Biol. 2006, 7, 391–403, doi:10.1038/nrm1939.
[52]
Gram Schjoldager, K.T.; Vester-Christensen, M.B.; Goth, C.K.; Petersen, T.N.; Brunak, S.; Bennett, E.P.; Levery, S.B.; Clausen, H. O-glycosylation modulates proprotein convertase activation of angiopoietin-like protein 3 - possible role of polypeptide GalNAc-transferase-2 in regulation of concentrations of plasma lipids. J. Biol. Chem. 2010, 285, 36293–36303.
[53]
Kato, K.; Jeanneau, C.; Tarp, M.A.; Benet-Pages, A.; Lorenz-Depiereux, B.; Bennett, E. P.; Mandel, U.; Strom, T. M.; Clausen, H. Polypeptide GalNAc-transferase T3 and familial tumoral calcinosis. Secretion of fibroblast growth factor 23 requires O-glycosylation. J. Biol. Chem. 2006, 281, 18370–18377.
[54]
Gill, D.; Clausen, H.; Bard, F. Location, location, location: new insights into O-GalNAc protein glycosylation. Trends Cell Biol. 2010, 23, 149–158.
[55]
Schwientek, T.; Bennett, E.P.; Flores, C.; Thacker, J.; Hollmann, M.; Reis, C.A.; Behrens, J.; Mandel, U.; Keck, B.; Schafer, M.A.; et al. Functional conservation of subfamilies of putative UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferases in Drosophila, Caenorhabditis elegans, and mammals. One subfamily composed of l(2)35Aa is essential in Drosophila. J. Biol. Chem. 2002, 277, 22623–22638.
Carlstedt, I.; Sheehan, J.K.; Corfield, A.P.; Gallagher, J.T. Mucous glycoproteins: A gel of a problem. Essays Biochem. 1985, 20, 40–76.
[58]
Taylor-Papadimitriou, J.; Burchell, J.; Miles, D.W.; Dalziel, M. MUC1 and cancer. Biochim. Biophys. Acta 1999, 1455, 301–313.
[59]
Park, J.H.; Nishidate, T.; Kijima, K.; Ohashi, T.; Takegawa, K.; Fujikane, T.; Hirata, K.; Nakamura, Y.; Katagiri, T. Critical roles of mucin 1 glycosylation by transactivated polypeptide N-acetylgalactosaminyltransferase 6 in mammary carcinogenesis. Cancer Res. 2010, 70, 2759–2769.
[60]
Pedersen, J.W.; Blixt, O.; Bennett, E.P.; Tarp, M.A.; Dar, I.; Mandel, U.; Poulsen, S.S.; Pedersen, A.E.; Rasmussen, S.; Jess, P.; et al. Seromic profi ling of colorectal cancer patients with novel glycopeptide microarray. Int. J. Cancer 2011, 128, 1860–1871.
[61]
Plummer, T.H. Jr.; Elder, J. H.; Alexander, S.; Phelan, A.W.; Tarentino, A.L. Demonstration of peptide: N-glycosidase F activity in endo-beta-N-acetylglucosaminidase F preparations. J. Biol. Chem. 1984, 259, 10700–10704.
Wada, Y.; Dell, A.; Haslam, S.M.; Tissot, B.; Canis, K.; Azadi, P.; Backstrom, M.; Costello, C.E.; Hansson, G.C.; Hiki, Y.; et al. Comparison of methods for profi ling O-glycosylation: Human Proteome Organisation Human Disease Glycomics/Proteome Initiative multi-institutional study of IgA1. Mol. Cell. Proteomics 2010, 9, 719–727, doi:10.1074/mcp.M900450-MCP200.
[64]
Carlson, D.M. Structures and immunochemical properties of oligosaccharides isolated from pig submaxillary mucins. J. Biol. Chem. 1968, 243, 616–626.
[65]
Babu, P.; North, S. J.; Jang-Lee, J.; Chalabi, S.; Mackerness, K.; Stowell, S. R.; Cummings, R. D.; Rankin, S.; Dell, A.; Haslam, S. M. Structural characterization of neutrophil glycans by ultra sensitive mass spectrometric glycomics methodology. Glycoconj. J. 2009, 26, 975–986, doi:10.1007/s10719-008-9146-4.
[66]
Nairn, A.V.; Aoki, K.; Dela Rosa, M.; Porterfield, M.; Lim, J.M.; Kulik, M.; Pierce, J.M.; Wells, L.; Dalton, S.; Tiemeyer, M.; et al. Regulation of Glycan Structures in Murine Embryonic Stem Cells: Combined Transcript Profiling of Glycan-Related Genes and Glycan Structural Analysis. J. Biol. Chem. 2012, 287, 37835–37856.
[67]
Maniatis, S.; Zhou, H.; Reinhold, V. Rapid de-O-glycosylation concomitant with peptide labeling using microwave radiation and an alkyl amine base. Anal. Chem. 2010, 82, 2421–2425, doi:10.1021/ac902734w.
[68]
Huang, Y.; Mechref, Y.; Novotny, M.V. Microscale nonreductive release of O-linked glycans for subsequent analysis throught MALDI mass spectrometry and capillary electrophoresis. Anal. Chem. 2001, 73, 6063–6069, doi:10.1021/ac015534c.
[69]
Yu, G.; Zhang, Y.; Zhang, Z.; Song, L.; Wang, P.; Chai, W. Effect and limitation of excess ammonium on the release of O-glycans in reducing forms from glycoproteins under mild alkaline conditions for glycomic and functional analysis. Anal. Chem. 2010, 82, 9534–9542.
[70]
Patel, T.; Bruce, J.; Merry, A.; Bigge, C.; Wormald, M.; Jaques, A.; Parekh, R. Use of hydrazine to release in intact and unreduced form both N- and. O-Linked oligosaccharides from glycoproteins. Biochemistry 1993, 32, 679–693.
[71]
Merry, A.H.; Neville, D.C.; Royle, L.; Matthews, B.; Harvey, D.J.; Dwek, R.A.; Rudd, P.M. Recovery of intact 2-aminobenzamide-labeled O-glycans released from glycoproteins by hydrazinolysis. Anal. Biochem. 2002, 304, 91–99, doi:10.1006/abio.2002.5620.
[72]
Tateno, H.; Toyota, M.; Saito, S.; Onuma, Y.; Ito, Y.; Hiemori, K.; Fukumura, M.; Nakasu, A.; Nakanishi, M.; Ohnuma, K.; et al. Glycome diagnosis of human induced pluripotent stem cells using lectin microarray. J. Biol. Chem. 2011, 286, 20345–20353.
[73]
Takasaki, S.; Mizuochi, T.; Kobata, A. Hydrazinolysis of asparagine-linked sugar chains to produce free oligosaccharides. Methods Enzymol. 1982, 83, 263–268, doi:10.1016/0076-6879(82)83019-X.
[74]
Kawashima, H.; Murata, T.; Yamamoto, K.; Tateishi, A.; Irimura, T.; Osawa, T. A simple method for the release of asparagine-linked oligosaccharides from a glycoprotein purified by SDS-polyacrylamide gel electrophoresis. J. Biochem. 1992, 111, 620–622.
[75]
Zauner, G.; Koeleman, C.A.; Deelder, A.M.; Wuhrer, M. Mass spectrometric O-glycan analysis after combined O-glycan release by β-elimination and 1-phenyl-3-methyl-5-pyrazolone labeling. Biochim. Biophys. Acta 2011, 1820, 1420–1428.
[76]
Wang, C.; Fan, W.; Zhang, P.; Wang, Z.; Huang, L. One-pot nonreductive O-glycan release and labeling with 1-phenyl-3-methyl-5-pyrazolone followed by ESI-MS analysis. Proteomics 2011, 11, 4229–4242, doi:10.1002/pmic.201000677.
[77]
Furukawa, J.-i.; Fujitani, N.; Araki, K.; Takegawa, Y.; Kodama, K.; Shinohara, Y. A versatile method for analysis of serine/threonine posttranslational modifications by β-elimination in the presence of pyrazolone analogues. Anal. Chem. 2011, 83, 9060–9067.
[78]
Hédou, J.; Bastide, B.; Page, A.; Michalski, J.C.; Morelle, W. Mapping of O-linked beta-N-acetylglucosamine modification sites in key contractile proteins of rat skeletal muscle. Proteomics 2009, 9, 2139–2148, doi:10.1002/pmic.200800617.
[79]
Jang, H.; Kim, T.W.; Yoon, S.; Choi, S.Y.; Kang, T.W.; Kim, S.Y.; Kwon, Y.W.; Cho, E.J.; Youn, H.D. O-GlcNAc regulates pluripotency and reprogramming by directly acting on core components of the pluripotency network. Cell Stem Cell 2012, 11, 62–74, doi:10.1016/j.stem.2012.03.001.
[80]
Trinidad, J.C.; Barkan, D.T.; Gulledge, B.F.; Thalhammer, A.; Sali, A.; Schoepfer, R.; Burlingame, A.L. Global identification and characterization of both O-glcNAcylation and phosphorylation at the murine synapse. Mol. Cell Proteomics 2012, 11, 215–229, doi:10.1074/mcp.O112.018366.
Zauner, G.; Kozak, R.P.; Gardner, R.A.; Fernandes, D.L.; Deelder, A.M.; Wuhrer, M. Protein O-glycosylation analysis. Biol. Chem. 2012, 393, 687–708.
[83]
Robinson, L.N.; Artpradit, C.; Raman, R.; Shriver, Z.H.; Ruchirawat, M.; Sasisekharan, R. Harnessing glycomics technologies: integrating structure with function for glycan characterization. Electrophoresis 2012, 33, 797–814.
[84]
Hakomori, S. Structure and function of glycosphingolipids and sphingolipids: Recollections and future trends. Biochim. Biophy. Acta 2008, 1780, 325–346, doi:10.1016/j.bbagen.2007.08.015.
[85]
Lahiri, S.; Futerman, A.H. The metabolism and function of sphingolipids and glycosphingolipids. Cell Mol. Life Sci. 2007, 64, 2270–2284, doi:10.1007/s00018-007-7076-0.
[86]
Hoetzl, S.; Sprong, H.; van Meer, G. van Meer, G. The way we view cellular (glyco)sphingolipids. J. Neurochem. 2007, 103, 3–13, doi:10.1111/j.1471-4159.2007.04721.x.
[87]
Hakomori, S.; Handa, K.; Iwabuchi, K.; Yamamura, S.; Prinetti, A. New insights in glycosphingolipid function: ‘‘glycosignaling domain,’’ a cell surface assembly of glycosphingolipids with signal transducer molecules, involved in cell adhesion coupled with signaling. Glycobiology 1998, 8, xi–xix, doi:10.1093/oxfordjournals.glycob.a018822.
[88]
Sorice, M.; Longo, A.; Garofalo, T.; Mattei, V.; Misasi, R.; Pavan, A. Role of GM3-enriched microdomains in signal transduction regulation in T lymphocytes. Glycoconj. J. 2004, 20, 63–70.
[89]
Yu, S.; Withers, D.A.; Hakomori, S. Globoside-dependent adhesion of human embryonal carcinoma cells, based on carbohydrate-carbohydrate interaction, initiates signal transduction and induces enhanced activity of transcription factors AP1 and CREB. Biol. Chem. 1998, 273, 2517–2525, doi:10.1074/jbc.273.5.2517.
[90]
Todeschini, A.R.; Hakomori, S.I. Functional role of glycosphingolipids and gangliosides in control of cell adhesion, motility, and growth through glycosynaptic microdomains. Biochim. Biophys. Acta 2008, 1780, 421–433, doi:10.1016/j.bbagen.2007.10.008.
[91]
Merrill, A.H. Jr. Sphingolipid and glycosphingolipid metabolic pathways in the era of sphingolipidomics. Chem Rev. 2011, 111, 6387–6422, doi:10.1021/cr2002917.
[92]
Chang, W.W.; Lee, C.H.; Lee, P.; Lin, J.; Hsu, C.W.; Hung, J.T.; Lin, J.J.; Yu, J.C.; Shao, L.E.; Yu, J.; et al. Expression of Globo H and SSEA3 in breast cancer stem cells and the involvement of fucosyl transferases 1 and 2 in Globo H synthesis. Proc. Natl. Acad. Sci. USA 2008, 105, 11667–11672.
[93]
Liang, Y.J.; Kuo, H.H.; Lin, C.H.; Chen, Y.Y.; Yang, B.C.; Cheng, Y.Y.; Yu, A.L.; Khoo, K.H.; Yu, J. Switching of the core structures of glycosphingolipids from globo- and lacto- to ganglio-series upon human embryonic stem cell differentiation. Proc. Natl. Acad. Sci. USA 2010, 107, 22564–22569.
[94]
Heimburg-Molinaro, J.; Lum, M.; Vijay, G.; Jain, M.; Almogren, A.; Rittenhouse-Olson, K. Cancer vaccines and carbohydrate epitopes. Vaccine 2011, 29, 8802–8826.
[95]
Wuhrer, M. Glycomics using mass spectrometry. Glycoconj. J. 2013, 30, 11–22, doi:10.1007/s10719-012-9376-3.
[96]
Merrill, A.H. Jr.; Sullards, M.C.; Allegood, J.C.; Kelly, S.; Wang, E. Sphingolipidomics: High-throughput, structure-specific, and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometry. Methods 2005, 36, 207–224, doi:10.1016/j.ymeth.2005.01.009.
[97]
Ciucanu, I.; Kerek, F. A simple and rapid method for the permethylation of carbohydrates. Carbohydr. Res. 1984, 131, 209–217, doi:10.1016/0008-6215(84)85242-8.
Muthing, J.; Distler, U. Advances on the compositional analysis of glycosphingolipids combining thin-layer chromatography with mass spectrometry. Mass. Spectrom. Rev. 2010, 29, 425–479.
[100]
Flanqea, C.; Serb, A.; Sisu, E.; Zamfir, A.D. Reprint of: Chip-based nanoelectrospray mass spectrometry of brain gangliosides. Biochim. Biophy. Acta 2011, 1811, 897–917, doi:10.1016/j.bbalip.2011.09.006.
[101]
Gupta, V.; Bhinge, K.N.; Hosain, S.B.; Xiong, K.; Gu, X.; Shi, R.; Ho, M.Y.; Khoo, K.H.; Li, S.C.; et al. Ceramide glycosylation by glucosylceramide synthase selectively maintains the properties of breast cancer stem cells. J. Biol. Chem. 2012, 287, 37195–37205.
[102]
Sisu, E.; Flangea, C.; Serb, A.; Rizzi, A.; Zamfir, A.D. High-performance separation techniques hyphenated to mass spectrometry for ganglioside analysis. Electrophoresis 2011, 32, 1591–1609.
[103]
Ikeda, K.; Shimizu, T.; Taguchi, R. Targeted analysis of ganglioside and sulfatide molecular species by LC/ESI-MS/MS with theoretically expanded multiple reaction monitoring. J. Lipid Res. 2008, 49, 2678–2689, doi:10.1194/jlr.D800038-JLR200.
[104]
Ikeda, K.; Taguchi, R. Highly sensitive localization analysis of gangliosides and sulfatides including structural isomers in mouse cerebellum sections by combination of laser microdissection and hydrophilic interaction liquid chromatography/electrospray ionization mass spectrometry with theoretically expanded multiple reaction monitoring. Rapid Commun. Mass Spectrom. 2010, 24, 2957–2965, doi:10.1002/rcm.4716.
[105]
Li, S.C.; DeGasperi, R.; Muldrey, J.E.; Li, Y.T. A unique glycosphingolipid-splitting enzyme (ceramide-glycanase from leech) cleaves the linkage between the oligosaccharide and the ceramide. Biochem. Biophys. Res. Commun. 1986, 141, 346–352, doi:10.1016/S0006-291X(86)80375-8.
[106]
Zhou, B.; Li, S.C.; Laine, R.A.; Huang, R.T.; Li, Y.T. Isolation and characterization of ceramide glycanase from the leech, Macrobdella decora. J. Biol. Chem. 1989, 264, 12272–12277.
[107]
Li, Y.T.; Ishikawa, Y.; Li, S.C. Occurrence of ceramide-glycanase in the earthworm; Lumbricus terrestris. Biochem. Biophys. Res. Commun. 1987, 149, 167–172, doi:10.1016/0006-291X(87)91619-6.
[108]
Ito, M.; Yamagata, T. A novel glycosphingolipid-degrading enzyme cleaves the linkage between the oligosaccharide and ceramide of neutral and acidic glycosphingolipids. J. Biol. Chem. 1986, 261, 14278–14282.
[109]
Ito, M.; Yamagata, T. Purification; characterization of glycosphingolipid-specific endoglycosidases (endoglycoceramidases) from a mutant strain of Rhodococcus sp. Evidence for three molecular species of endoglycoceramidase with different specificities. J. Biol. Chem. 1989, 264, 9510–9519.
[110]
Ashida, H.; Yamamoto, K.; Kumagai, H.; Tochikura, T. Purification; characterization of membrane-bound endoglycoceramidase from Corynebacterium sp. Eur. J. Biochem. 1992, 205, 729–735, doi:10.1111/j.1432-1033.1992.tb16836.x.
[111]
Ishibashi, Y.; Kobayashi, U.; Hijikata, A.; Sakaguchi, K.; Goda, H.M.; Tamura, T.; Okino, N.; Ito, M. Preparation and characterization of EGCase I, applicable to the comprehensive analysis of GSLs, using a rhodococcal expression system. J. Lipid. Res. 2012, 53, 2242–2251, doi:10.1194/jlr.D028951.
[112]
Fujitani, N.; Takegawa, Y.; Ishibashi, Y.; Araki, K.; Furukawa, J.; Mitsutake, S.; Igarashi, Y.; Ito, M.; Shinohara, Y. Qualitative and quantitative cellular glycomics of glycosphingolipids based on rhodococcal endoglycosylceramidase-assisted glycan cleavage; glycoblotting-assisted sample preparation; and matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometry analysis. J. Biol. Chem. 2011, 286, 41669–41679.
[113]
Heiskanen, A.; Hirvonen, T.; Salo, H.; Impola, U.; Olonen, A.; Laitinen, A.; Tiitinen, S.; Natunen, S.; Aitio, O.; Miller-Podraza, H.; et al. Glycomics of bone marrow-derived mesenchymal stem cells can be used to evaluate their cellular differentiation stage. Glycoconj. J. 2009, 26, 367–384, doi:10.1007/s10719-008-9217-6.
[114]
Hakomori, S. Release of carbohydrates from sphingoglycolipid by osmium-catalyzed periodate oxidation, followed by treatment with mild alkali. J. Lipid Res. 1966, 7, 789–792.
[115]
MacDonald, D.L.; Patt, L.M.; Hakomori, S. Notes on improved procedures for the chemical modification and degradation of glycosphingolipids. J. Lipid Res. 1980, 21, 642–645.
[116]
Mylvaganam, M.; Meng, L.; Lingwood, C.A. Oxidation of glycosphingolipids under basic conditions: synthesis of glycosyl “serine acids” as opposed to “ceramide acids”. Precursors for neoglycoconjugates with increased ligand binding affinity. Biochemistry 1999, 38, 10885–10897, doi:10.1021/bi990669m.
[117]
Yowler, B.C.; Stoehr, S.A.; Schengrund, C.L. Oxidation and base-catalyzed elimination of the saccharide portion of GSLs having very different polarities. J. Lipid Res. 2001, 42, 659–662.
Purushothaman, A.; Sugahara, K.; Faissner, A. Chondroitin sulfate "wobble motifs" modulate maintenance and differentiation of neural stem cells and their progeny. J. Biol. Chem. 2012, 287, 2935–2942, doi:10.1074/jbc.R111.298430.
[122]
Quantock, A.J.; Young, R.D.; Akama, T.O. Structural and biochemical aspects of keratan sulphate in the cornea. Cell Mol. Life Sci. 2010, 67, 891–906, doi:10.1007/s00018-009-0228-7.
[123]
Ly, M.; Leach, F.E., 3rd.; Laremore, T.N.; Toida, T.; Amster, I.J.; Linhardt, R.J. The proteoglycan bikunin has a defined sequence. Nat. Chem. Biol. 2011, 7, 827–833, doi:10.1038/nchembio.673.
Guimond, S.E.; Puvirajesinghe, T,M.; Skidmore, M.A.; Kalus, I.; Dierks, T.; Yates, E.A.; Turnbull, J.E. Rapid purification and high sensitivity analysis of heparan sulfate from cells and tissues: toward glycomics profiling. J. Biol. Chem. 2009, 284, 25714–25722.
[126]
Zhao, X.; Yang, B.; Datta, P.; Gasmili, L.; Zhang, F.; Linhard, R.J. Cell-based microscale isolation of glycoaminoglycans for glycomics study. J. Carbohydr. Chem. 2012, 31, 420–435, doi:10.1080/07328303.2012.658126.
[127]
Takegawa, Y.; Araki, K.; Fujitani, N.; Furukawa, J.; Sugiyama, H.; Sakai, H.; Shinohara, Y. Simultaneous analysis of heparan sulfate; chondroitin/dermatan sulfates; and hyaluronan disaccharides by glycoblotting-assisted sample preparation followed by single-step zwitter-ionic-hydrophilic interaction chromatography. Anal. Chem. 2011, 83, 9443–9449.
[128]
Izumikawa, T.; Uyama, T.; Okuura, Y.; Sugahara, K.; Kitagawa, H. Involvement of chondroitin sulfate synthase-3 (chondroitin synthase-2) in chondroitin polymerization through its interaction with chondroitin synthase-1 or chondroitin-polymerizing factor. Biochem. J. 2007, 403, 545–552, doi:10.1042/BJ20061876.
Linhardt, R.J.; Rice, K.G.; Kim, Y.S.; Lohse, D.L.; Wang, H.M.; Loganathan, D. Mapping and quantification of the major oligosaccharide components of heparin. Biochem. J. 1988, 254, 781–787.
[131]
Kitagawa, H.; Kinoshita, A.; Sugahara, K. Microanalysis of glycosaminoglycan-derived disaccharides labeled with the fluorophore 2-aminoacridone by capillary electrophoresis and high-performance liquid chromatography. Anal. Biochem. 1995, 232, 114–121, doi:10.1006/abio.1995.9952.
[132]
Militsopoulou, M.; Lamari, F.N.; Hjerpe, A.; Karamanos, N.K. Determination of twelve heparin- and heparan sulfate-derived disaccharides as 2-aminoacridone derivatives by capillary zone electrophoresis using ultraviolet and laser-induced fluorescence detection. Electrophoresis 2002, 23, 1104–1109, doi:10.1002/1522-2683(200204)23:7/8<1104::AID-ELPS1104>3.0.CO;2-1.
[133]
Kinoshita, A.; Sugahara, K. Microanalysis of glycosaminoglycan-derived oligosaccharides labeled with a fluorophore 2-aminobenzamide by high-performance liquid chromatography: application to disaccharide composition analysis and exosequencing of oligosaccharides. Anal. Biochem. 1999, 269, 367–378, doi:10.1006/abio.1999.4027.
[134]
Turnbull, J.E.; Hopwood, J.J.; Gallagher, J.T. A strategy for rapid sequencing of heparan sulfate and heparin saccharides. Proc. Natl. Acad. Sci. USA 1999, 96, 2698–2703.
[135]
Skidmore, M.A.; Guimond, S.E.; Dumax-Vorzet, A.F.; Yates, E.A.; Turnbull, J.E. Disaccharide compositional analysis of heparan sulfate and heparin polysaccharides using UV or high-sensitivity fluorescence (BODIPY) detection. Nat. Protoc. 2010, 5, 1983–1992, doi:10.1038/nprot.2010.145.
[136]
Lawrence, R.; Olson, S.K.; Steele, R.E.; Wang, L.; Warrior, R.; Cummings, R.D.; Esko, J.D. Evolutionary differences in glycosaminoglycan fine structure detected by quantitative glycan reductive isotope labeling. J. Biol. Chem. 2008, 283, 33674–33684.
[137]
Hitchcock, A.M.; Yates, K.E.; Costello, C.E.; Zaia, J. Comparative glycomics of connective tissue glycosaminoglycans. Proteomics 2008, 8, 1384–1397, doi:10.1002/pmic.200700787.
[138]
Bowman, M.J.; Zaia, J. Comparative glycomics using a tetraplex stable-isotope coded tag. Anal. Chem. 2010, 82, 3023–3031, doi:10.1021/ac100108w.
[139]
Hitchkock, A.M.; Bowman, M.J.; Staples, G.O.; Zaia, J. Improved workup for glycosaminoglycan disaccharide analysis using CE with LIF detection. Electrophoresis 2008, 29, 4538–4548, doi:10.1002/elps.200800335.
[140]
Eldridge, S.L.; Higgins, L.A.; Dickey, B.J.; Larive, C.K. Insights into the capillary electrophoresis separation of heparin disaccharides from nuclear magnetic resonance, pKa, and electrophoretic mobility measurement. Anal. Chem. 2009, 81, 7406–7415.
[141]
Plaas, A.H.; West, L.A.; Midura, R.J. Keratan sulfate disaccharide composition determined by FACE analysis of keratanase II and endo-beta-galactosidase digestion products. Glycobiology 2001, 10, 779–790, doi:10.1093/glycob/11.10.779.
[142]
Korir, A.K.; Limtiaco, J.F.; Gutierrez, S.M.; Larive, C.K. Ultraperformance ion-pair liquid chromatography coupled to electrospray time-of-flight mass spectrometry for compositional profiling and quantification of heparin and heparan sulfate. Anal. Chem. 2008, 80, 1297–1306.
[143]
Imanari, T.; Toida, T.; Koshiishi, I.; Toyoda, H. High-performance liquid chromatographic analysis of glycosaminoglycan-derived oligosaccharides. J. Chromatogr. A 1996, 720, 275–293, doi:10.1016/0021-9673(95)00338-X.
[144]
Jones, C.J.; Membreno, N.; Larive, C.K. Insights into the mechanism of separation of heparin and heparan sulfate disaccharides by reverse-phase ion-pair chromatography. J. Chromatogr. A 2010, 1217, 479–488, doi:10.1016/j.chroma.2009.11.064.
[145]
Staples, G.O.; Shi, X.; Zaia, J. Extended N-sulfated domains reside at the nonreducing end of heparan sulfate chains. J. Biol. Chem. 2010, 285, 18336–18343, doi:10.1074/jbc.M110.101592.
[146]
Volpi, N. High-performance liquid chromatography and on-line mass spectrometry detection for the analysis of chondroitin sulfates/hyaluronan disaccharides derivatized with 2-aminoacridone. Anal. Biochem. 2010, 397, 12–23, doi:10.1016/j.ab.2009.09.030.
[147]
Yang, B.; Chang, Y.; Weyers, A.M.; Sterner, E.; Linhardt, R.J. Disaccharide analysis of glycosaminoglycan mixtures by ultra-high-performance liquid chromatography-mass spectrometry. J. Chromatogr. A 2012, 1225, 91–98, doi:10.1016/j.chroma.2011.12.063.
[148]
Laremore, T.N.; Leach, F.E., 3rd.; Solakyildirim, K.; Amster, I.J.; Linhardt, R.J. Glycosaminoglycan characterization by electrospray ionization mass spectrometry including fourier transform mass spectrometry. Methods Enzymol. 2010, 478, 79–108, doi:10.1016/S0076-6879(10)78003-4.
[149]
Uygun, B.E.; Stojsih, S.E.; Matthew, H.W. Effects of immobilized glycosaminoglycans on the proliferation and differentiation of mesenchymal stem cells. Tissue Eng. Part A 2009, 15, 3499–3512, doi:10.1089/ten.tea.2008.0405.
[150]
Kumarasuriyar, A.; Murali, S.; Nurcombe, V.; Cool, S.M. Glycosaminoglycan composition changes with MG-63 osteosarcoma osteogenesis in vitro and induces human mesenchymal stem cell aggregation. J. Cell Physiol. 2009, 218, 501–511, doi:10.1002/jcp.21620.
[151]
Dombrowski, C.; Song, S.J.; Chuan, P.; Lim, X.; Susanto, E.; Sawyer, A.A.; Woodruff, M.A.; Hutmacher, D.W.; Nurcombe, V.; Cool, S.M. Heparan sulfate mediates the proliferation and differentiation of rat mesenchymal stem cells. Stem Cells Dev. 2009, 18, 661–670, doi:10.1089/scd.2008.0157.
[152]
Nairn, A.V.; Kinoshita-Toyoda, A.; Toyoda, H.; Xie, J.; Harris, K.; Dalton, S.; Kulik, M.; Pierce, J.M.; Toida, T.; Moremen, K.W.; et al. Glycomics of proteoglycan biosynthesis in murine embryonic stem cell differentiation. J. Proteome Res. 2007, 6, 4374–4387, doi:10.1021/pr070446f.
[153]
Kawabe, K.; Tateyama, D.; Toyoda, H.; Kawasaki, N.; Hashii, N.; Nakao, H.; Matsumoto, S.; Nonaka, M.; Matsumura, H.; Hirose, Y.; et al. Novel Antibody for Human Induced Pluripotent Stem (hiPS) Cells and Embryonic Stem (ES) Cells Recognizes a Type of Keratan Sulfate Lacking Oversulfated Structures. Glycobiology 2012, 23, 322–336.
[154]
Toida, T.; Hileman, R.E.; Smith, A.E.; Vlahova, P.I.; Linhardt, R.J. Enzymatic preparation of heparin oligosaccharides containing antithrombin III binding sites. J. Biol. Chem. 1996, 271, 32040–32947.
[155]
Ly, M.; Laremore, T.N.; Linhardt, R.J. Proteoglycomics: recent progress and future challenges. OMICS 2010, 14, 389–399, doi:10.1089/omi.2009.0123.
[156]
Lawrence, R.; Brown, J.R.; Al-Mafraji, K.; Lamanna, W.C,; Beitel, J.R.; Boons, G.J.; Esko, J.D.; Crawford, B.E. Disease-specific non-reducing end carbohydrate biomarkers for mucopolysaccharidoses. Nat. Chem. Biol. 2012, 8, 197–204.
[157]
Wearne, K.A.; Winter, H.C.; O'Shea, K.; Goldstein, I.J. Use of lectins for probing differentiated human embryonic stem cells for carbohydrates. Glycobiology 2006, 16, 981–990, doi:10.1093/glycob/cwl019.
[158]
Toyoda, M.; Yamazaki-Inoue, M.; Itakura, Y.; Kuno, A.; Ogawa, T.; Yamada, M.; Akutsu, H.; Takahashi, Y.; Kanzaki, S.; Narimatsu, H.; et al. Lectin microarray analysis of pluripotent and multipotent stem cells. Genes Cells 2011, 16, 1–11.
[159]
Wang, Y.C.; Nakagawa, M.; Garitaonandia, I.; Slavin, I.; Altun, G.; Lacharite, R.M.; Nazor, K.L.; Tran, H.T.; Lynch, C.L.; Leonardo, T.R.; et al. Specific lectin biomarkers for isolation of human pluripotent stem cells identified through array-based glycomic analysis. Cell Res. 2011, 21, 1551–1563, doi:10.1038/cr.2011.148.
[160]
Yasuda, E.; Tateno, H.; Hirabayashi, J.; Iino, I.; Sako, T. Lectin microarray reveals binding profiles of Lactobacillus casei strains in a comprehensive analysis of bacterial cell wall polysaccharides. Appl. Eviron Microbiol. 2011, 77, 4539–4546, doi:10.1128/AEM.00240-11.
[161]
Parry, S.; Ledger, V.; Tissot, B.; Haslam, S.M.; Scott, J.; Morris, H.R. Integrated mass spectrometric strategy for characterizing the glycans from glycosphingolipids and glycoproteins: direct identification of sialyl Lex in mice. Glycobiology 2007, 17, 646–654, doi:10.1093/glycob/cwm024.
