Structural remodeling of proteoglycans on retinoic acid-induced differentiation of NCCIT cells

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Authors
Gasimli, Leyla
Stansfield, Hope E.
Nairn, Alison V.
Liu, Haiying
Paluh, Janet L.
Yang, Bo
Dordick, Jonathan S.
Moremen, Kelley W.
Linhardt, Robert J.
Issue Date
2013-07-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Abstract
Pluripotent and multipotent cells become increasingly lineage restricted through differentiation. Alterations to the cellular proteoglycan composition and structure should accompany these changes to influence cell proliferation, delineation of tissues and acquisition of cell migration capabilities. Retinoic acid plays an important role in pre-patterning of the early embryo. Retinoic acid can be used in vitro to induce differentiation, causing pluripotent and multipotent cells to become increasingly lineage restricted. We examined retinoic acid-induced changes in the cellular proteoglycan composition of the well-characterized teratocarcinoma line NCCIT. Our analysis revealed changes in the abundance of transcripts for genes encoding core proteins, enzymes that are responsible for early and late linkage region biosynthesis, as well as enzymes for GAG chain extension and modification. Transcript levels for genes encoding core proteins used as backbones for polysaccharide synthesis revealed highly significant increases in expression of lumican and decorin, 1,500-fold and 2,800-fold, respectively. Similarly, glypican 3, glypican 5, versican and glypican 6 showed increases between 5 and 70-fold. Significant decreases in biglycan, serglycin, glypican 4, aggrecan, neurocan, CD74 and glypican 1 were observed. Disaccharide analysis of the glycans in heparin/heparan sulfate and chondroitin/dermatan sulfate revealed retinoic acid-induced changes restricted to chondroitin/dermatan sulfate glycans. Our study provides the first detailed analysis of changes in the glycosaminoglycan profile of human pluripotent cells upon treatment with the retinoic acid morphogen.
Description
Glycoconjugate Journal, 30, 497–510
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Full Citation
Structural remodeling of proteoglycans on retinoic acid-induced differentiation of NCCIT cells, H. E. Stansfield, L. Gasimli, A. V. Nairn, H. Liu, J. L. Paluh, B. Yang, M. J. Saunders, J. S. Dordick, K. W. Moremen, R. J. Linhardt, Glycoconjugate Journal, 30, 497–510, 2013.
Publisher
Springer
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DOI
ISSN
15734986
2820080
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