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dc.contributor.authorJohnson, Claire E
dc.contributor.authorCrawford, Brett E
dc.contributor.authorStavridis, Marios
dc.contributor.authorTen Dam, Gerdy
dc.contributor.authorWat, Annie L
dc.contributor.authorRushton, Graham
dc.contributor.authorWard, Christopher M
dc.contributor.authorWilson, Valerie A
dc.contributor.authorVan Kuppevelt, Toin H
dc.contributor.authorEsko, Jeffrey D
dc.contributor.authorSmith, Austin
dc.contributor.authorGallagher, John T
dc.contributor.authorMerry, Catherine L R
dc.date.accessioned2009-06-23T12:00:08Z
dc.date.available2009-06-23T12:00:08Z
dc.date.issued2007-08
dc.identifier.citationEssential alterations of heparan sulfate during the differentiation of embryonic stem cells to Sox1-enhanced green fluorescent protein-expressing neural progenitor cells. 2007, 25 (8):1913-23 Stem Cellsen
dc.identifier.issn1066-5099
dc.identifier.pmid17464092
dc.identifier.doi10.1634/stemcells.2006-0445
dc.identifier.urihttp://hdl.handle.net/10541/71228
dc.description.abstractEmbryonic stem (ES) cells can be cultured in conditions that either maintain pluripotency or allow differentiation to the three embryonic germ layers. Heparan sulfate (HS), a highly polymorphic glycosaminoglycan, is a critical cell surface coreceptor in embryogenesis, and in this paper we describe its structural transition from an unusually low-sulfated variant in ES cells to a more highly sulfated form in fluorescence-activated cell sorting-purified neural progenitor cells. The characteristic domain structure of HS was retained during this transformation. However, qualitative variations in surface sulfation patterns between ES and differentiated cells were revealed using HS epitope-specific antibodies and the HS-binding growth factor fibroblast growth factor 2 (FGF-2). Expression profiles of the HS modification enzymes indicated that both "early" (N-sulfotransferases) and "late" (6O- and 3O-sulfotransferases) sulfotransferases contributed to the alterations in sulfation patterning. An HS-null ES line was used to demonstrate the necessity for HS in neural differentiation. HS is a coreceptor for many of the protein effectors implicated in pluripotency and differentiation (e.g., members of the FGF family, bone morphogenic proteins, and fibronectin). We suggest that the stage-specific activities of these proteins are finely regulated by dynamic changes in sulfation motifs in HS chains. Disclosure of potential conflicts of interest is found at the end of this article.
dc.language.isoenen
dc.subject.meshAnimals
dc.subject.meshCell Differentiation
dc.subject.meshCells, Cultured
dc.subject.meshDNA-Binding Proteins
dc.subject.meshEmbryonic Stem Cells
dc.subject.meshFibroblast Growth Factor 2
dc.subject.meshGene Expression Regulation
dc.subject.meshGreen Fluorescent Proteins
dc.subject.meshHeparitin Sulfate
dc.subject.meshHigh Mobility Group Proteins
dc.subject.meshMice
dc.subject.meshMice, Knockout
dc.subject.meshNeurons
dc.subject.meshRecombinant Fusion Proteins
dc.subject.meshSOXB1 Transcription Factors
dc.subject.meshSulfates
dc.subject.meshTransfection
dc.subject.meshTubulin
dc.titleEssential alterations of heparan sulfate during the differentiation of embryonic stem cells to Sox1-enhanced green fluorescent protein-expressing neural progenitor cellsen
dc.typeArticleen
dc.contributor.departmentDepartment of Medical Oncology, Cancer Research UK, The University of Manchester, Manchester, UK.en
dc.identifier.journalStem Cellsen
html.description.abstractEmbryonic stem (ES) cells can be cultured in conditions that either maintain pluripotency or allow differentiation to the three embryonic germ layers. Heparan sulfate (HS), a highly polymorphic glycosaminoglycan, is a critical cell surface coreceptor in embryogenesis, and in this paper we describe its structural transition from an unusually low-sulfated variant in ES cells to a more highly sulfated form in fluorescence-activated cell sorting-purified neural progenitor cells. The characteristic domain structure of HS was retained during this transformation. However, qualitative variations in surface sulfation patterns between ES and differentiated cells were revealed using HS epitope-specific antibodies and the HS-binding growth factor fibroblast growth factor 2 (FGF-2). Expression profiles of the HS modification enzymes indicated that both "early" (N-sulfotransferases) and "late" (6O- and 3O-sulfotransferases) sulfotransferases contributed to the alterations in sulfation patterning. An HS-null ES line was used to demonstrate the necessity for HS in neural differentiation. HS is a coreceptor for many of the protein effectors implicated in pluripotency and differentiation (e.g., members of the FGF family, bone morphogenic proteins, and fibronectin). We suggest that the stage-specific activities of these proteins are finely regulated by dynamic changes in sulfation motifs in HS chains. Disclosure of potential conflicts of interest is found at the end of this article.


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