Changes in glycosaminoglycan structure on differentiation of human embryonic stem cells towards mesoderm and endoderm lineages

Gasimli, Leyla
Hickey, Anne Marie
Yang, Bo
Li, Guoyun
Dela Rosa, Mitche
Nairn, Alison V.
Kulik, Michael J.
Dordick, Jonathan S.
Moremen, Kelley W.
Dalton, Stephen
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Changes in glycosaminoglycan structure on differentiation of human embryonic stem cells towards mesoderm and endoderm lineages, L. Gasimli, A. M. Hickey, B. Yang, G. Li, M. dela Rosa, A. V. Nairn, M. J. Kulik, J. S. Dordick, K. W. Moremen, S. Dalton, R. J. Linhardt, Biochemica et Biophysica Acta, 1840, 1993–2003, 2014.
Background: Proteoglycans are found on the cell surface and in the extracellular matrix, and serve as prime sites for interaction with signaling molecules. Proteoglycans help regulate pathways that control stem cell fate, and therefore represent an excellent tool to manipulate these pathways. Despite their importance, there is a dearth of data linking glycosaminoglycan structure within proteoglycans with stem cell differentiation. Methods: Human embryonic stem cell line WA09 (H9) was differentiated into early mesoderm and endoderm lineages, and the glycosaminoglycanomic changes accompanying these transitions were studied using transcript analysis, immunoblotting, immunofluorescence and disaccharide analysis. Results: Pluripotent H9 cell lumican had no glycosaminoglycan chains whereas in splanchnic mesoderm lumican was glycosaminoglycanated. H9 cells have primarily non-sulfated heparan sulfate chains. On differentiation towards splanchnic mesoderm and hepatic lineages N-sulfo group content increases. Differences in transcript expression of NDST1, HS6ST2 and HS6ST3, three heparan sulfate biosynthetic enzymes, within splanchnic mesoderm cells compared to H9 cells correlate to changes in glycosaminoglycan structure. Conclusions: Differentiation of embryonic stem cells markedly changes the proteoglycanome. General significance: The glycosaminoglycan biosynthetic pathway is complex and highly regulated, and therefore, understanding the details of this pathway should enable better control with the aim of directing stem cell differentiation.
Biochemica et Biophysica Acta, 1840, 1993–2003
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The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Biochimica et Biophysica Acta - General Subjects
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