title: Changes in glycosphingolipid composition during differentiation of human embryonic stem cells to ectodermal or endodermal lineages.
abstract: Glycosphingolipids (GSLs) are ubiquitous components of cell membranes that can act as mediators of cell adhesion and signal transduction and can possibly be used as cell type-specific markers. Our previous study indicated that there was a striking switch in the core structures of GSLs during differentiation of human embryonic stem cells (hESCs) into embryoid body (EB), suggesting a close association of GSLs with cell differentiation. In this study, to further clarify if alterations in GSL patterns are correlated with lineage-specific differentiation of hESCs, we analyzed changes in GSLs as hESCs were differentiated into neural progenitors or endodermal cells by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and tandem mass spectrometry (MS/MS) analyses. During hESC differentiation into neural progenitor cells, we found that the core structures of GSLs switched from globo- and lacto- to mostly ganglio-series dominated by GD3. On the other hand, when hESCs were differentiated into endodermal cells, patterns of GSLs totally differed from those observed in EB outgrowth and neural progenitors. The most prominent GSL identified by the MALDI-MS and MS/MS analysis was Gb(4) Ceramide, with no appreciable amount of stage-specific embryonic antigens 3 or 4, or GD3, in endodermal cells. These changes in GSL profiling were accompanied by alterations in the biosynthetic pathways of expressions of key glycosyltransferases. Our findings suggest that changes in GSLs are closely associated with lineage specificity and differentiation of hESCs.
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Yuh-Jin
authors.initials: YJ
authors.lastname: Liang
authors.forename: Bei-Chia
authors.initials: BC
authors.lastname: Yang
authors.forename: Jin-Mei
authors.initials: JM
authors.lastname: Chen
authors.forename: Yu-Hsing
authors.initials: YH
authors.lastname: Lin
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Huang
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Cheng
authors.forename: Chi-Yen
authors.initials: CY
authors.lastname: Hsu
authors.forename: Kay-Hooi
authors.initials: KH
authors.lastname: Khoo
authors.forename: Chia-Ning
authors.initials: CN
authors.lastname: Shen
authors.forename: John
authors.initials: J
authors.lastname: Yu
mesh_terms: D002454:Cell Differentiation; D019070:Cell Lineage; D004475:Ectoderm / Q000166:cytology* / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D004707:Endoderm / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005732:Gangliosides / Q000378:metabolism; D005915:Globosides / Q000378:metabolism; D006028:Glycosphingolipids / Q000378:metabolism*; D016695:Glycosyltransferases / Q000378:metabolism; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D005732:Gangliosides; D005915:Globosides; D006028:Glycosphingolipids; C024032:globotetraosylceramide; C026226:ganglioside, GD3; D016695:Glycosyltransferases