{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T03:40:27Z","timestamp":1776051627024,"version":"3.50.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,10,19]],"date-time":"2015-10-19T00:00:00Z","timestamp":1445212800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,10,19]],"date-time":"2015-10-19T00:00:00Z","timestamp":1445212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Glycosphingolipids (GSLs) are glycoconjugates that function as mediators of cell adhesion and modulators of signal transduction. Some well-defined markers of undifferentiated human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) are glycoconjugates, such as SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81. However, Comprehensive GSL profiles of hiPSCs have not yet been elucidated. The global images of GSLs from the parental cells, hiPSCs and differentiated cells revealed that there are parental cell-independent specific glycolipids, including Globo H (fucosyl-Gb5Cer) and H type1 antigen (fucosyl-Lc4Cer) that are novel markers for undifferentiated hiPSCs. Interestingly, undifferentiated hiPSCs expressed H type 1 antigen, specific for blood type O, regardless of the cells\u2019 genotypes. Thus, in this study, we defined the dynamics of GSL remodeling during reprogramming from parental cell sets to iPSC sets and thence to iPSC-neural cells.<\/jats:p>","DOI":"10.1038\/srep14988","type":"journal-article","created":{"date-parts":[[2015,10,19]],"date-time":"2015-10-19T09:37:39Z","timestamp":1445247459000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Glycolipid dynamics in generation and differentiation of induced pluripotent stem cells"],"prefix":"10.1038","volume":"5","author":[{"given":"Takuma","family":"Ojima","sequence":"first","affiliation":[]},{"given":"Eri","family":"Shibata","sequence":"additional","affiliation":[]},{"given":"Shiho","family":"Saito","sequence":"additional","affiliation":[]},{"given":"Masashi","family":"Toyoda","sequence":"additional","affiliation":[]},{"given":"Hideki","family":"Nakajima","sequence":"additional","affiliation":[]},{"given":"Mayu","family":"Yamazaki-Inoue","sequence":"additional","affiliation":[]},{"given":"Yoshitaka","family":"Miyagawa","sequence":"additional","affiliation":[]},{"given":"Nobutaka","family":"Kiyokawa","sequence":"additional","affiliation":[]},{"given":"Jun-ichiro","family":"Fujimoto","sequence":"additional","affiliation":[]},{"given":"Toshinori","family":"Sato","sequence":"additional","affiliation":[]},{"given":"Akihiro","family":"Umezawa","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2015,10,19]]},"reference":[{"key":"BFsrep14988_CR1","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","volume":"131","author":"K Takahashi","year":"2007","unstructured":"Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861\u2013872 (2007).","journal-title":"Cell"},{"key":"BFsrep14988_CR2","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1126\/science.1151526","volume":"318","author":"J Yu","year":"2007","unstructured":"Yu, J. et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917\u20131920 (2007).","journal-title":"Science"},{"key":"BFsrep14988_CR3","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1038\/labinvest.2011.85","volume":"91","author":"KE Hankowski","year":"2011","unstructured":"Hankowski, K. E., Hamazaki, T., Umezawa, A. & Terada, N. Induced pluripotent stem cells as a next-generation biomedical interface. Lab Invest 91, 972\u2013977 (2011).","journal-title":"Lab Invest"},{"key":"BFsrep14988_CR4","doi-asserted-by":"publisher","first-page":"10231","DOI":"10.1073\/pnas.172380699","volume":"99","author":"S Hakomori","year":"2002","unstructured":"Hakomori, S. Glycosylation defining cancer malignancy: new wine in an old bottle. Proc Natl Acad Sci USA 99, 10231\u201310233 (2002).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep14988_CR5","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.bbagen.2007.08.015","volume":"1780","author":"SI Hakomori","year":"2008","unstructured":"Hakomori, S. I. Structure and function of glycosphingolipids and sphingolipids: recollections and future trends. Biochim Biophys Acta 1780, 325\u2013346 (2008).","journal-title":"Biochim Biophys Acta"},{"key":"BFsrep14988_CR6","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1016\/j.febslet.2009.10.065","volume":"584","author":"SI Hakomori","year":"2010","unstructured":"Hakomori, S. I. Glycosynaptic microdomains controlling tumor cell phenotype through alteration of cell growth, adhesion and motility. FEBS Lett 584, 1901\u20131906 (2010).","journal-title":"FEBS Lett"},{"key":"BFsrep14988_CR7","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1111\/gtc.12003","volume":"17","author":"Y Nishijima","year":"2012","unstructured":"Nishijima, Y. et al. Glycan profiling of endometrial cancers using lectin microarray. Genes Cells 17, 826\u2013836 (2012).","journal-title":"Genes Cells"},{"key":"BFsrep14988_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1365-2443.2010.01459.x","volume":"16","author":"M Toyoda","year":"2011","unstructured":"Toyoda, M. et al. Lectin microarray analysis of pluripotent and multipotent stem cells. Genes Cells 16, 1\u201311 (2011).","journal-title":"Genes Cells"},{"key":"BFsrep14988_CR9","doi-asserted-by":"publisher","first-page":"265","DOI":"10.5966\/sctm.2012-0154","volume":"2","author":"H Tateno","year":"2013","unstructured":"Tateno, H. et al. Podocalyxin is a glycoprotein ligand of the human pluripotent stem cell-specific probe rBC2LCN. Stem Cells Transl Med 2, 265\u2013273 (2013).","journal-title":"Stem Cells Transl Med"},{"key":"BFsrep14988_CR10","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.carres.2012.08.003","volume":"361","author":"Y Wang","year":"2012","unstructured":"Wang, Y. et al. Glycosylation of Nalpha-lauryl-O-(beta-D-xylopyranosyl)-L-serinamide as a saccharide primer in cells. Carbohydr Res 361, 33\u201340 (2012).","journal-title":"Carbohydr Res"},{"key":"BFsrep14988_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4052\/tigg.19.1","volume":"19","author":"T Sato","year":"2007","unstructured":"Sato, T., Hatanaka, K., Hashimoto, H. & Yamagata, T. Syntheses of oligosaccharides using cell function. Trends in Glycoscience and Glycotechnology 19, 1\u201317 (2007).","journal-title":"Trends in Glycoscience and Glycotechnology"},{"key":"BFsrep14988_CR12","first-page":"1279","volume":"37","author":"T Kaneko","year":"2010","unstructured":"Kaneko, T. et al. Neuroblastoma cells can be classified according to glycosphingolipid expression profiles identified by liquid chromatography-tandem mass spectrometry. Int J Oncol 37, 1279\u20131288 (2010).","journal-title":"Int J Oncol"},{"key":"BFsrep14988_CR13","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1093\/jb\/mvq142","volume":"149","author":"N Ogasawara","year":"2011","unstructured":"Ogasawara, N. et al. Accelerated biosynthesis of neolacto-series glycosphingolipids in differentiated mouse embryonal carcinoma F9 cells detected by using dodecyl N-acetylglucosaminide as a saccharide primer. J Biochem 149, 321\u2013330 (2011).","journal-title":"J Biochem"},{"key":"BFsrep14988_CR14","doi-asserted-by":"publisher","first-page":"3519","DOI":"10.1002\/elps.200800719","volume":"30","author":"X Zhu","year":"2009","unstructured":"Zhu, X., Hatanaka, K., Yamagata, T. & Sato, T. Structural analysis of glycosphingolipid analogues obtained by the saccharide primer method using CE-ESI-MS. Electrophoresis 30, 3519\u20133526 (2009).","journal-title":"Electrophoresis"},{"key":"BFsrep14988_CR15","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1073\/pnas.1214233110","volume":"110","author":"N Fujitani","year":"2013","unstructured":"Fujitani, N. et al. Total cellular glycomics allows characterizing cells and streamlining the discovery process for cellular biomarkers. Proc Natl Acad Sci USA 110, 2105\u20132110 (2013).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep14988_CR16","doi-asserted-by":"publisher","first-page":"22564","DOI":"10.1073\/pnas.1007290108","volume":"107","author":"YJ Liang","year":"2010","unstructured":"Liang, Y. J. et al. 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 107, 22564\u201322569 (2010).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep14988_CR17","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.1002\/stem.750","volume":"29","author":"YJ Liang","year":"2011","unstructured":"Liang, Y. J. et al. Changes in glycosphingolipid composition during differentiation of human embryonic stem cells to ectodermal or endodermal lineages. Stem Cells 29, 1995\u20132004 (2011).","journal-title":"Stem Cells"},{"key":"BFsrep14988_CR18","doi-asserted-by":"publisher","first-page":"10035","DOI":"10.1074\/jbc.M112.436162","volume":"288","author":"A Barone","year":"2013","unstructured":"Barone, A. et al. Structural complexity of non-acid glycosphingolipids in human embryonic stem cells grown under feeder-free conditions. J Biol Chem 288, 10035\u201310050 (2013).","journal-title":"J Biol Chem"},{"key":"BFsrep14988_CR19","doi-asserted-by":"publisher","first-page":"2355","DOI":"10.1002\/j.1460-2075.1983.tb01746.x","volume":"2","author":"R Kannagi","year":"1983","unstructured":"Kannagi, R. et al. 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\u20132361 (1983).","journal-title":"Embo j"},{"key":"BFsrep14988_CR20","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.legalmed.2011.10.002","volume":"14","author":"T Muro","year":"2012","unstructured":"Muro, T. et al. Determination of ABO genotypes by real-time PCR using allele-specific primers. Leg Med (Tokyo) 14, 47\u201350 (2012).","journal-title":"Leg Med (Tokyo)"},{"key":"BFsrep14988_CR21","doi-asserted-by":"publisher","first-page":"2857","DOI":"10.1038\/nprot.2007.407","volume":"2","author":"M Ota","year":"2007","unstructured":"Ota, M., Fukushima, H., Kulski, J. K. & Inoko, H. Single nucleotide polymorphism detection by polymerase chain reaction-restriction fragment length polymorphism. Nat Protoc 2, 2857\u20132864 (2007).","journal-title":"Nat Protoc"},{"key":"BFsrep14988_CR22","doi-asserted-by":"publisher","first-page":"e1002085","DOI":"10.1371\/journal.pgen.1002085","volume":"7","author":"K Nishino","year":"2011","unstructured":"Nishino, K. et al. DNA Methylation Dynamics in Human Induced Pluripotent Stem Cells over Time. PLoS Genet 7, e1002085 (2011).","journal-title":"PLoS Genet"},{"key":"BFsrep14988_CR23","doi-asserted-by":"publisher","first-page":"e13017","DOI":"10.1371\/journal.pone.0013017","volume":"5","author":"K Nishino","year":"2010","unstructured":"Nishino, K. et al. Defining hypo-methylated regions of stem cell-specific promoters in human iPS cells derived from extra-embryonic amnions and lung fibroblasts. PLoS One 5, e13017 (2010).","journal-title":"PLoS One"},{"key":"BFsrep14988_CR24","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1097\/TP.0b013e31818a6805","volume":"86","author":"J M\u00f6lne","year":"2008","unstructured":"M\u00f6lne, J. et al. Blood group ABO antigen expression in human embryonic stem cells and in differentiated hepatocyte- and cardiomyocyte-like cells. Transplantation 86, 1407\u20131413 (2008).","journal-title":"Transplantation"},{"key":"BFsrep14988_CR25","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1038\/nbt.1947","volume":"29","author":"C Tang","year":"2011","unstructured":"Tang, C. et al. An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells. Nat Biotechnol 29, 829\u2013834 (2011).","journal-title":"Nat Biotechnol"},{"key":"BFsrep14988_CR26","doi-asserted-by":"publisher","first-page":"11667","DOI":"10.1073\/pnas.0804979105","volume":"105","author":"WW Chang","year":"2008","unstructured":"Chang, W. W. 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 105, 11667\u201311672 (2008).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep14988_CR27","doi-asserted-by":"publisher","first-page":"11661","DOI":"10.1073\/pnas.0804923105","volume":"105","author":"CC Wang","year":"2008","unstructured":"Wang, C. C. et al. Glycan microarray of Globo H and related structures for quantitative analysis of breast cancer. Proc Natl Acad Sci USA 105, 11661\u201311666 (2008).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep14988_CR28","doi-asserted-by":"publisher","first-page":"2727","DOI":"10.1016\/j.yexcr.2009.06.016","volume":"315","author":"H Makino","year":"2009","unstructured":"Makino, H. et al. Mesenchymal to embryonic incomplete transition of human cells by chimeric OCT4\/3 (POU5F1) with physiological co-activator EWS. Exp Cell Res 315, 2727\u20132740 (2009).","journal-title":"Exp Cell Res"},{"key":"BFsrep14988_CR29","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/nbt.1529","volume":"27","author":"SM Chambers","year":"2009","unstructured":"Chambers, S. M. et al. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 27, 275\u2013280 (2009).","journal-title":"Nat Biotechnol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep14988.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep14988","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/srep14988","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/www.nature.com\/articles\/srep14988.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T15:42:09Z","timestamp":1672933329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep14988"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,19]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,12,7]]}},"alternative-id":["BFsrep14988"],"URL":"https:\/\/doi.org\/10.1038\/srep14988","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,19]]},"assertion":[{"value":"23 October 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 September 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 October 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14988"}}