title: Changes in glycosaminoglycan structure on differentiation of human embryonic stem cells towards mesoderm and endoderm lineages.
abstract: BACKGROUND
  Proteoglycans are found on the cell surface and in the extracellular matrix, and serve as prime sites for interaction with signaling molecules. Proteoglycans help regulate pathways that control stem cell fate, and therefore represent an excellent tool to manipulate these pathways. Despite their importance, there is a dearth of data linking glycosaminoglycan structure within proteoglycans with stem cell differentiation.
  
  
  METHODS
  Human embryonic stem cell line WA09 (H9) was differentiated into early mesoderm and endoderm lineages, and the glycosaminoglycanomic changes accompanying these transitions were studied using transcript analysis, immunoblotting, immunofluorescence and disaccharide analysis.
  
  
  RESULTS
  Pluripotent H9 cell lumican had no glycosaminoglycan chains whereas in splanchnic mesoderm lumican was glycosaminoglycanated. H9 cells have primarily non-sulfated heparan sulfate chains. On differentiation towards splanchnic mesoderm and hepatic lineages N-sulfo group content increases. Differences in transcript expression of NDST1, HS6ST2 and HS6ST3, three heparan sulfate biosynthetic enzymes, within splanchnic mesoderm cells compared to H9 cells correlate to changes in glycosaminoglycan structure.
  
  
  CONCLUSIONS
  Differentiation of embryonic stem cells markedly changes the proteoglycanome.
  
  
  CONCLUSIONS
  The glycosaminoglycan biosynthetic pathway is complex and highly regulated, and therefore, understanding the details of this pathway should enable better control with the aim of directing stem cell differentiation.
authors.affiliation: Department of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
authors.forename: Leyla
authors.initials: L
authors.lastname: Gasimli
authors.affiliation: Department of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Hickey
authors.affiliation: Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
authors.forename: Guoyun
authors.initials: G
authors.lastname: Li
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
authors.forename: Mitche
authors.initials: M
authors.lastname: dela Rosa
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
authors.forename: Alison V
authors.initials: AV
authors.lastname: Nairn
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kulik
authors.affiliation: Department of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA; Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA; Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA; Department of Materials Science and Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Dordick
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
authors.forename: Kelley W
authors.initials: KW
authors.lastname: Moremen
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Dalton
authors.affiliation: Department of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA; Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA; Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA; Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. Electronic address: linhar@rpi.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
mesh_terms: D002454:Cell Differentiation; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology*; D004707:Endoderm / Q000166:cytology*; D006025:Glycosaminoglycans / Q000096:biosynthesis / Q000737:chemistry*; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D008648:Mesoderm / Q000166:cytology*; D011509:Proteoglycans / Q000737:chemistry
chemical_list: D006025:Glycosaminoglycans; D011509:Proteoglycans
keywords: Embryonic; Glycosaminoglycan; Hepatocytes; Proteoglycans; Splanchnic mesoderm; Stem cells