Using embryonic stem cells to understand how glycosaminoglycans regulate differentiation.
Differentiation and subsequent specialization of every cell within an organism is an intricate interwoven process. A complex network of signalling pathways eventually leads to the specification of a multitude of different cell types able to function co-operatively. HS (heparan sulfate) is a highly sulfated linear polysaccharide that resides at the pericellular cell-matrix interface where it dictates the binding and activity of a large number of proteins, including growth factors and morphogens such as members of the FGF (fibroblast growth factor) and BMP (bone morphogenetic protein) families. Embryonic stem cells derived from mice with mutations in components of the HS biosynthetic pathway provide an opportunity to dissect the contribution of HS to signalling pathways critical for regulating stem cell maintenance and differentiation. In addition to improving our understanding of signalling mechanisms, this knowledge enables the selection of exogenous HS saccharides to improve the efficiency and selectivity of directed differentiation protocols, offering a cost-effective alternative to high concentrations of expensive growth factors to drive differentiation towards a particular therapeutically relevant cell type.
*Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, Michael Smith Building, University of Manchester, Oxford Road, Manchester M13 9PT, U.K.
Rebecca J
RJ
Holley
†Stem Cell Glycobiology Group, School of Materials, University of Manchester, Grosvenor Street, Manchester M1 7HS, U.K.
Kate A
KA
Meade
†Stem Cell Glycobiology Group, School of Materials, University of Manchester, Grosvenor Street, Manchester M1 7HS, U.K.
Catherine L R
CL
Merry
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000166:cytology*; D006025:Glycosaminoglycans / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D051379:Mice
D006025:Glycosaminoglycans