title: The Lewis X-related α1,3-fucosyltransferase, Fut10, is required for the maintenance of stem cell populations.
abstract: Lewis X (Le(X), Galβ1-4(Fucα1-3)GlcNAc) is a carbohydrate epitope that is present at the nonreducing terminus of sugar chains of glycoproteins and glycolipids, and is abundantly expressed in several stem cell populations. Le(X) antigen can be used in conjunction with fluorescence-activated cell sorting to isolate neurosphere-forming neural stem cells (NSCs) from embryonic mouse brains. However, its function in the maintenance and differentiation of stem cells remains largely unknown. In this study, we examined mice deficient for fucosyltransferase 9 (Fut9), which is thought to synthesize most, if not all, of the Le(X) moieties in the brain. We found that the number of NSCs was increased in the brain of Fut9(-/-) embryos, suggesting that Fut9-synthesized Le(X) is dispensable for the maintenance of NSCs. Another α1,3-fucosyltransferase gene, fucosyltransferase 10 (Fut10), is expressed in the ventricular zone of the embryonic brain. Overexpression of Fut10 enhanced the self-renewal of NSCs. Conversely, suppression of Fut10 expression induced the differentiation of NSCs and embryonic stem cells. In addition, knockdown of Fut10 expression in the cortical ventricular zone of the embryonic brain by in utero electroporation of Fut10-miRNAs impaired the radial migration of neural precursor cells. Our data suggest that Fut10 is involved in a unique α1,3-fucosyltransferase activity with stringent substrate specificity, and that this activity is required to maintain stem cells in an undifferentiated state.
authors.affiliation: From the Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, and.
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Kumar
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Torii
authors.forename: Yugo
authors.initials: Y
authors.lastname: Ishino
authors.forename: Daisuke
authors.initials: D
authors.lastname: Muraoka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshimura
authors.forename: Akira
authors.initials: A
authors.lastname: Togayachi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narimatsu
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikenaka
authors.forename: Seiji
authors.initials: S
authors.lastname: Hitoshi
mesh_terms: D000818:Animals; D019556:COS Cells; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D002522:Chlorocebus aethiops; D004622:Embryo, Mammalian / Q000166:cytology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000201:enzymology; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D016256:Lewis X Antigen / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000201:enzymology*; D011134:Polysaccharides / Q000378:metabolism
chemical_list: D016256:Lewis X Antigen; D035683:MicroRNAs; D011134:Polysaccharides; D005647:Fucosyltransferases; C584674:Fut10 protein, mouse; C031692:galactoside 3-fucosyltransferase
keywords: Bisecting N-Glycans; Embryonic Stem Cell; Glycobiology; Glycosyltransferases; HPLC; Neural Stem Cell; Stemness