FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins

• Published in: Stem cell reports 2018-08, Vol.11 (2), p.325-333
• Main Authors: Awan, Baarkullah, Turkov, David, Schumacher, Cameron, Jacobo, Antonio, McEnerney, Amber, Ramsey, Ashley, Xu, Gege, Park, Dayoung, Kalomoiris, Stefanos, Yao, Wei, Jao, Li-En, Allende, Miguel L., Lebrilla, Carlito B., Fierro, Fernando A.
• Format: Article
• Language: English
• Subjects: Animals; Cell Movement - genetics; core fucosylation; Fibroblast Growth Factor 2 - chemistry; Fibroblast Growth Factor 2 - metabolism; FUT8; Gene Expression Profiling; Gene Expression Regulation; Glycosylation; Humans; Integrins - chemistry; Integrins - metabolism; mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mice; migration; Models, Molecular; Molecular Conformation; MSC; multipotent stromal cells; Polysaccharides - chemistry; Polysaccharides - metabolism; Structure-Activity Relationship
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2018.06.007

Since hundreds of clinical trials are investigating the use of multipotent stromal cells (MSCs) for therapeutic purposes, effective delivery of the cells to target tissues is critical. We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits. Gain- and loss-of-function experiments show that FUT8 is both necessary and sufficient to induce migration of MSCs. Silencing FUT8 also affects migration of MSCs in zebrafish embryos and a murine bone fracture model. Finally, we use in silico modeling to show that core fucosylations restrict the degrees of freedom of glycans on the integrin’s surface, hence stabilizing glycans on a specific position. Altogether, we show a mechanism whereby FGF2 promotes migration of MSCs by modifying N-glycans. This work may help improve delivery of MSCs in therapeutic settings. [Display omitted] •FGF2 upregulates FUT8 and core fucosylations in MSCs•FUT8 is both necessary and sufficient to promote migration of MSCs•Core fucosylations stabilize the position of N-glycans on integrins In this article, Fierro and colleagues used RNA-seq and mass spectrometry to find that FGF2 induces migration of MSCs by inducing expression of FUT8, which leads to more core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits. This affects cell migration in zebrafish embryos and toward bone fracture in mice.