FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins
Summary: 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 o...
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Elsevier
2018-08-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671118302704 |
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doaj-ce444aabfa97499b803810207be599ce2020-11-24T21:17:19ZengElsevierStem Cell Reports2213-67112018-08-01112325333FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of IntegrinsBaarkullah Awan0David Turkov1Cameron Schumacher2Antonio Jacobo3Amber McEnerney4Ashley Ramsey5Gege Xu6Dayoung Park7Stefanos Kalomoiris8Wei Yao9Li-En Jao10Miguel L. Allende11Carlito B. Lebrilla12Fernando A. Fierro13Institute for Regenerative Cures, University of California, Davis, Sacramento, CA, USAInstitute for Regenerative Cures, University of California, Davis, Sacramento, CA, USAInstitute for Regenerative Cures, University of California, Davis, Sacramento, CA, USAInstitute for Regenerative Cures, University of California, Davis, Sacramento, CA, USAInstitute for Regenerative Cures, University of California, Davis, Sacramento, CA, USAInstitute for Regenerative Cures, University of California, Davis, Sacramento, CA, USADepartment of Chemistry, University of California, Davis, Davis, CA, USADepartment of Chemistry, University of California, Davis, Davis, CA, USAInstitute for Regenerative Cures, University of California, Davis, Sacramento, CA, USACenter for Musculoskeletal Health, Department of Internal Medicine, University of California, Davis, Davis, CA, USADepartment of Cell Biology and Human Anatomy, University of California, Davis, Davis, CA, USADepartment of Cell Biology and Human Anatomy, University of California, Davis, Davis, CA, USA; Center for Genome Regulation, Facultad de Ciencias, Universidad de Chile, Santiago, ChileDepartment of Chemistry, University of California, Davis, Davis, CA, USAInstitute for Regenerative Cures, University of California, Davis, Sacramento, CA, USA; Department of Cell Biology and Human Anatomy, University of California, Davis, Davis, CA, USA; Corresponding authorSummary: 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. : 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. Keywords: core fucosylation, migration, FUT8, MSC, multipotent stromal cells, mesenchymal stem cellshttp://www.sciencedirect.com/science/article/pii/S2213671118302704 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Baarkullah Awan David Turkov Cameron Schumacher Antonio Jacobo Amber McEnerney Ashley Ramsey Gege Xu Dayoung Park Stefanos Kalomoiris Wei Yao Li-En Jao Miguel L. Allende Carlito B. Lebrilla Fernando A. Fierro |
| spellingShingle |
Baarkullah Awan David Turkov Cameron Schumacher Antonio Jacobo Amber McEnerney Ashley Ramsey Gege Xu Dayoung Park Stefanos Kalomoiris Wei Yao Li-En Jao Miguel L. Allende Carlito B. Lebrilla Fernando A. Fierro FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins Stem Cell Reports |
| author_facet |
Baarkullah Awan David Turkov Cameron Schumacher Antonio Jacobo Amber McEnerney Ashley Ramsey Gege Xu Dayoung Park Stefanos Kalomoiris Wei Yao Li-En Jao Miguel L. Allende Carlito B. Lebrilla Fernando A. Fierro |
| author_sort |
Baarkullah Awan |
| title |
FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins |
| title_short |
FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins |
| title_full |
FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins |
| title_fullStr |
FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins |
| title_full_unstemmed |
FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins |
| title_sort |
fgf2 induces migration of human bone marrow stromal cells by increasing core fucosylations on n-glycans of integrins |
| publisher |
Elsevier |
| series |
Stem Cell Reports |
| issn |
2213-6711 |
| publishDate |
2018-08-01 |
| description |
Summary: 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. : 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. Keywords: core fucosylation, migration, FUT8, MSC, multipotent stromal cells, mesenchymal stem cells |
| url |
http://www.sciencedirect.com/science/article/pii/S2213671118302704 |
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