Essential alterations of heparan sulfate during the differentiation of embryonic stem cells to Sox1-enhanced green fluorescent protein-expressing neural progenitor cells

2.50
Hdl Handle:
http://hdl.handle.net/10541/71228
Title:
Essential alterations of heparan sulfate during the differentiation of embryonic stem cells to Sox1-enhanced green fluorescent protein-expressing neural progenitor cells
Authors:
Johnson, Claire E; Crawford, Brett E; Stavridis, Marios; Ten Dam, Gerdy; Wat, Annie L; Rushton, Graham; Ward, Christopher M; Wilson, Valerie A; Van Kuppevelt, Toin H; Esko, Jeffrey D; Smith, Austin; Gallagher, John T; Merry, Catherine L R
Abstract:
Embryonic 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.
Affiliation:
Department of Medical Oncology, Cancer Research UK, The University of Manchester, Manchester, UK.
Citation:
Essential 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 Cells
Journal:
Stem Cells
Issue Date:
Aug-2007
URI:
http://hdl.handle.net/10541/71228
DOI:
10.1634/stemcells.2006-0445
PubMed ID:
17464092
Type:
Article
Language:
en
ISSN:
1066-5099
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
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.en
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

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