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

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    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
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    Affiliation
    Department of Medical Oncology, Cancer Research UK, The University of Manchester, Manchester, UK.
    Issue Date
    2007-08
    
    Metadata
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    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.
    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
    URI
    http://hdl.handle.net/10541/71228
    DOI
    10.1634/stemcells.2006-0445
    PubMed ID
    17464092
    Type
    Article
    Language
    en
    ISSN
    1066-5099
    ae974a485f413a2113503eed53cd6c53
    10.1634/stemcells.2006-0445
    Scopus Count
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    All Paterson Institute for Cancer Research

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