Glycomics of Proteoglycan Biosynthesis in Murine Embryonic Stem Cell Differentiation
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Authors
Nairn, Alison V.
Kinoshita-Toyoda, Akiko
Toyoda, Hidenao
Xie, Jin
Harris, Kyle
Dalton, Stephen
Kulik, Michael
Pierce, J. Michael
Toida, Toshihiko
Moremen, Kelley W.
Issue Date
2007-11-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Glycosaminoglycans (GAGs) play a critical role in binding and activation of growth factors involved in cell signaling critical for developmental biology. The biosynthetic pathways for GAGs have been elucidated over the past decade and now analytical methodology makes it possible to determine GAG composition in as few as 10 million cells. A glycomics approach was used to examine GAG content, composition, and the level of transcripts encoding for GAG biosynthetic enzymes as murine embryonic stem cells (mESCs) differentiate to embryoid bodies (EBs) and to extraembryonic endodermal cells (ExE) to better understand the role of GAGs in stem cell differentiation. Hyaluronan synthesis was enhanced by 13- and 24-fold, most likely due to increased expression of hyaluronan synthase-2. Chondroitin sulfate (CS)/dermatan sulfate (DS) synthesis was enhanced by 4- and 6-fold, and heparan sulfate (HS) synthesis was enhanced by 5- and 8-fold following the transition from mESC to EB and ExE. Transcripts associated with the synthesis of the early precursors were largely unaltered, suggesting other factors account for enhanced GAG synthesis. The composition of both CS/DS and HS also changed upon differentiation. Interestingly, CS type E and highly sulfated HS both increase as mESCs differentiate to EBs and ExE. Differentiation was also accompanied by enhanced 2-sulfation in both CS/DS and HS families. Transcript levels for core proteins generally showed increases or remained constant upon mESC differentiation. Finally, transcripts encoding selected enzymes and isoforms, including GlcNAc-4,6-O-sulfotransferase, C5-epimerases, and 3-O-sulfotransferases involved in late GAG biosynthesis, were also enriched. These biosynthetic enzymes are particularly important in introducing GAG fine structure, essential for intercellular communication, cell adhesion, and outside-in signaling. Knowing the changes in GAG fine structure should improve our understanding the biological properties of differentiated stem cells.
Description
Journal of Proteome Research 6, 4374-4387
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Glycomics of Proteoglycan Biosynthesis in Murine Embryonic Stem Cell Differentiation, A. V. Nairn, A. Kinoshita-Toyoda, H. Toyoda, J. Xie, K. Harris, S. Dalton, M. Kulik, J. M. Pierce, T. Toida, K. W. Moremen, R. J. Linhardt, Journal of Proteome Research 6, 4374-4387, 2007.
Publisher
American Chemical Society (ACS)
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
15353893