ES (embryonic stem) cell differentiation is dependent on the presence of HS (heparan sulfate). We have demonstrated that, during differentiation, the evolution of specific cell lineages is associated with particular patterns of GAG (glycosaminoglycan) expression. For example, different HS epitopes are synthesized during neural or mesodermal lineage formation. Cell lines mutant for various components of the HS biosynthetic pathway are selectively impaired in their differentiation, with lineage-specific effects observed for some lines. We have also observed that the addition of soluble GAG saccharides to cells, with or without cell-surface HS, can influence the pace and outcome of differentiation, again highlighting specific pattern requirements for particular lineages. We are combining this work with ongoing studies into the design of artificial cell environments where we have optimized three-dimensional scaffolds, generated by electrospinning or by the formation of hydrogels, for the culture of ES cells. By permeating these scaffolds with defined GAG oligosaccharides, we intend to control the mechanical environment of the cells (via the scaffold architecture) as well as their biological signalling environment (using the oligosaccharides). We predict that this will allow us to control ES cell pluripotency and differentiation in a three-dimensional setting, allowing the generation of differentiated cell types for use in drug discovery/testing or in therapeutics.
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February 2011
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Conference Article|
January 19 2011
Glycosaminoglycans as regulators of stem cell differentiation
Raymond A.A. Smith;
Raymond A.A. Smith
1Stem Cell Glycobiology Group, Materials Science, University of Manchester, Manchester, M1 7HS, U.K.
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Kate Meade;
Kate Meade
1Stem Cell Glycobiology Group, Materials Science, University of Manchester, Manchester, M1 7HS, U.K.
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Claire E. Pickford;
Claire E. Pickford
1Stem Cell Glycobiology Group, Materials Science, University of Manchester, Manchester, M1 7HS, U.K.
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Rebecca J. Holley;
Rebecca J. Holley
1Stem Cell Glycobiology Group, Materials Science, University of Manchester, Manchester, M1 7HS, U.K.
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Catherine L.R. Merry
Catherine L.R. Merry
1
1Stem Cell Glycobiology Group, Materials Science, University of Manchester, Manchester, M1 7HS, U.K.
1To whom correspondence should be addressed (email Catherine.Merry@manchester.ac.uk).
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Publisher: Portland Press Ltd
Received:
October 29 2010
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem Soc Trans (2011) 39 (1): 383–387.
Article history
Received:
October 29 2010
Citation
Raymond A.A. Smith, Kate Meade, Claire E. Pickford, Rebecca J. Holley, Catherine L.R. Merry; Glycosaminoglycans as regulators of stem cell differentiation. Biochem Soc Trans 1 February 2011; 39 (1): 383–387. doi: https://doi.org/10.1042/BST0390383
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