Document Detail

Glycosaminoglycans as regulators of stem cell differentiation.
MedLine Citation:
PMID:  21265809     Owner:  NLM     Status:  MEDLINE    
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.
Raymond A A Smith; Kate Meade; Claire E Pickford; Rebecca J Holley; Catherine L R Merry
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical Society transactions     Volume:  39     ISSN:  1470-8752     ISO Abbreviation:  Biochem. Soc. Trans.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-26     Completed Date:  2011-04-26     Revised Date:  2011-10-27    
Medline Journal Info:
Nlm Unique ID:  7506897     Medline TA:  Biochem Soc Trans     Country:  England    
Other Details:
Languages:  eng     Pagination:  383-7     Citation Subset:  IM    
Stem Cell Glycobiology Group, Materials Science, University of Manchester, Manchester, M1 7HS, UK.
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MeSH Terms
Carbohydrate Conformation
Carbohydrate Sequence
Cell Differentiation / physiology*
Cell Line
Cell Lineage
Embryonic Stem Cells / physiology*
Glycosaminoglycans / chemistry,  metabolism*
Heparitin Sulfate / chemistry,  metabolism
Molecular Sequence Data
Tissue Culture Techniques
Grant Support
G0701165//Medical Research Council
Reg. No./Substance:
0/Glycosaminoglycans; 9050-30-0/Heparitin Sulfate

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