The GAGOme: a cell-based library of displayed glycosaminoglycans

Yen-Hsi Chen; Yoshiki Narimatsu; Thomas Mandel Clausen; Catarina Gomes; Richard Karlsson; Catharina Steentoft; Charlotte Bredo Spliid; Tobias Gustavsson; Ali Salanti; Andrea Persson; Anders Malmström; Daniel Willén; Ulf Ellervik; Eric Paul Bennett; Yang Mao; Henrik Clausen; Zhang Yang

doi:10.1038/s41592-018-0086-z

The GAGOme: a cell-based library of displayed glycosaminoglycans

Yen-Hsi Chen, Yoshiki Narimatsu, Thomas Mandel Clausen, Catarina Gomes, Richard Karlsson, Catharina Steentoft, Charlotte Bredo Spliid, Tobias Gustavsson, Ali Salanti, Andrea Persson, Anders Malmström, Daniel Willén, Ulf Ellervik, Eric Paul Bennett, Yang Mao, Henrik Clausen, Zhang Yang

36 Citations (Scopus)

Abstract

Glycosaminoglycans (GAGs) are essential polysaccharides in normal physiology and disease. However, understanding of the contribution of specific GAG structures to specific biological functions is limited, largely because of the great structural heterogeneity among GAGs themselves, as well as technical limitations in the structural characterization and chemical synthesis of GAGs. Here we describe a cell-based method to produce and display distinct GAGs with a broad repertoire of modifications, a library we refer to as the GAGOme. By using precise gene editing, we engineered a large panel of Chinese hamster ovary cells with knockout or knock-in of the genes encoding most of the enzymes involved in GAG biosynthesis, to generate a library of isogenic cell lines that differentially display distinct GAG features. We show that this library can be used for cell-based binding assays, recombinant expression of proteoglycans with distinct GAG structures, and production of distinct GAG chains on metabolic primers that may be used for the assembly of GAG glycan microarrays.

Original language	English
Journal	Nature Methods
Volume	15
Issue number	11
Pages (from-to)	881-888
ISSN	1548-7091
DOIs	https://doi.org/10.1038/s41592-018-0086-z
Publication status	Published - 1 Nov 2018

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Chen, Y.-H., Narimatsu, Y., Clausen, T. M., Gomes, C., Karlsson, R., Steentoft, C., Spliid, C. B., Gustavsson, T., Salanti, A., Persson, A., Malmström, A., Willén, D., Ellervik, U., Bennett, E. P., Mao, Y., Clausen, H., & Yang, Z. (2018). The GAGOme: a cell-based library of displayed glycosaminoglycans. Nature Methods, 15(11), 881-888. https://doi.org/10.1038/s41592-018-0086-z

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title = "The GAGOme: a cell-based library of displayed glycosaminoglycans",

abstract = "Glycosaminoglycans (GAGs) are essential polysaccharides in normal physiology and disease. However, understanding of the contribution of specific GAG structures to specific biological functions is limited, largely because of the great structural heterogeneity among GAGs themselves, as well as technical limitations in the structural characterization and chemical synthesis of GAGs. Here we describe a cell-based method to produce and display distinct GAGs with a broad repertoire of modifications, a library we refer to as the GAGOme. By using precise gene editing, we engineered a large panel of Chinese hamster ovary cells with knockout or knock-in of the genes encoding most of the enzymes involved in GAG biosynthesis, to generate a library of isogenic cell lines that differentially display distinct GAG features. We show that this library can be used for cell-based binding assays, recombinant expression of proteoglycans with distinct GAG structures, and production of distinct GAG chains on metabolic primers that may be used for the assembly of GAG glycan microarrays.",

author = "Yen-Hsi Chen and Yoshiki Narimatsu and Clausen, {Thomas Mandel} and Catarina Gomes and Richard Karlsson and Catharina Steentoft and Spliid, {Charlotte Bredo} and Tobias Gustavsson and Ali Salanti and Andrea Persson and Anders Malmstr{\"o}m and Daniel Will{\'e}n and Ulf Ellervik and Bennett, {Eric Paul} and Yang Mao and Henrik Clausen and Zhang Yang",

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doi = "10.1038/s41592-018-0086-z",

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AU - Chen, Yen-Hsi

AU - Narimatsu, Yoshiki

AU - Clausen, Thomas Mandel

AU - Gomes, Catarina

AU - Karlsson, Richard

AU - Steentoft, Catharina

AU - Spliid, Charlotte Bredo

AU - Gustavsson, Tobias

AU - Salanti, Ali

AU - Persson, Andrea

AU - Malmström, Anders

AU - Willén, Daniel

AU - Ellervik, Ulf

AU - Bennett, Eric Paul

AU - Mao, Yang

AU - Clausen, Henrik

AU - Yang, Zhang

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AB - Glycosaminoglycans (GAGs) are essential polysaccharides in normal physiology and disease. However, understanding of the contribution of specific GAG structures to specific biological functions is limited, largely because of the great structural heterogeneity among GAGs themselves, as well as technical limitations in the structural characterization and chemical synthesis of GAGs. Here we describe a cell-based method to produce and display distinct GAGs with a broad repertoire of modifications, a library we refer to as the GAGOme. By using precise gene editing, we engineered a large panel of Chinese hamster ovary cells with knockout or knock-in of the genes encoding most of the enzymes involved in GAG biosynthesis, to generate a library of isogenic cell lines that differentially display distinct GAG features. We show that this library can be used for cell-based binding assays, recombinant expression of proteoglycans with distinct GAG structures, and production of distinct GAG chains on metabolic primers that may be used for the assembly of GAG glycan microarrays.

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JO - Nature Methods

JF - Nature Methods

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ER -

The GAGOme: a cell-based library of displayed glycosaminoglycans

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