A mutant cell library for systematic analysis of heparan sulfate

Qiu, Hong
Shi, Songshan
Yue, Jingwen
Xin, Meng
Nairn, Alison V.
Lin, Lei
Liu, Xinyue
Li, Guoyun
Archer-Hartmann, Stephanie A.
Dela Rosa, Mitche
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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A mutant cell library for systematic analysis of heparan sulfate, H. Qiu, S. Shi, J. Yue, M. Xin, A. V. Nairn, L. Lin, X. Liu, G. Li, S. A. Archer-Hartmann, M. Dela Rosa, M. Galizzi, S. Wang, F. Zhang, P. Azadi, T. H. van Kuppevelt, W. V. Cardoso, K. Kimata, X. Ai, K. W. Moremen, J. Esko, R. J. Linhardt, L. Wang, Nature Methods, 15, 889-899, 2018.
Heparan sulfate (HS) is a complex linear polysaccharide that modulates a wide range of biological functions. Elucidating the structure–function relationship of HS has been challenging. Here we report the generation of an HS-mutant mouse lung endothelial cell library by systematic deletion of HS genes expressed in the cell. We used this library to (1) determine that the strictly defined fine structure of HS, not its overall degree of sulfation, is more important for FGF2–FGFR1 signaling; (2) define the epitope features of commonly used anti-HS phage display antibodies; and (3) delineate the fine inter-regulation networks by which HS genes modify HS and chain length in mammalian cells at a cell-type-specific level. Our mutant-cell library will allow robust and systematic interrogation of the roles and related structures of HS in a cellular context.
Nature Methods, 15, 889-899
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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
Nature Methods
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