title: Fucosyltransferase VII improves the function of selectin ligands on cord blood hematopoietic stem cells.
abstract: Selectins and their carbohydrate ligands mediate the homing of hematopoietic stem/progenitor cells (HSPCs) to the bone marrow. We have previously shown that ex vivo fucosylation of selectin ligands on HSPCs by α1,3 fucosyltransferase VI (FUT6) leads to improved human cord blood (CB)-HSPC engraftment in non-obese diabetic (NOD)/severe combined immune deficient (SCID) mice. In the present study, we determined whether surface fucosylation with α1,3 fucosyltransferase VII (FUT7), which is primarily expressed by hematopoietic cells, improves the function of selectin ligands on CB-HSPCs in comparison with FUT6. A saturating amount of either FUT6 or FUT7, which generates comparable levels of expression of fucosylated epitopes on CB CD34(+) cells, was used for these experiments. In vitro, FUT7-treated CB CD34(+) cells exhibited greater binding to P- or E-selectin than that of FUT6-treated CB CD34(+) cells under static or physiological flow conditions. In vivo, FUT7 treatment, like FUT6, improved the early engraftment of CB CD34(+) cells in the bone marrow of sublethally irradiated NOD/SCID interleukin (IL)-2Rγ(null) (NSG) mice. FUT7 also exhibited marginally-yet statistically significant-increased engraftment at 4 and 6 weeks after transplantation. In addition, FUT7-treated CB CD34(+) cells exhibited increased homing to the bone marrow of irradiated NSG mice relative to sham-treated cells. These data indicate that FUT7 is effective at improving the function of selectin ligands on CB-HSPCs in vitro and enhancing early engraftment of treated CB-HSPCs in the bone marrow of recipients.
authors.affiliation: Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei City, Anhui Province 230001, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wan
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Sato
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Miyaji
authors.forename: J Michael
authors.initials: JM
authors.lastname: McDaniel
authors.forename: Yuesi
authors.initials: Y
authors.lastname: Wang
authors.forename: Etsuji
authors.initials: E
authors.lastname: Kaneko
authors.forename: BreeAnna
authors.initials: B
authors.lastname: Gibson
authors.forename: Padmaja
authors.initials: P
authors.lastname: Mehta-D'Souza
authors.forename: Yiyuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Mikhail
authors.initials: M
authors.lastname: Dozmorov
authors.forename: Leonard P
authors.initials: LP
authors.lastname: Miller
authors.forename: Jean
authors.initials: J
authors.lastname: Goodman
authors.forename: Zimin
authors.initials: Z
authors.lastname: Sun
authors.forename: Lijun
authors.initials: L
authors.lastname: Xia
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D005647:Fucosyltransferases / Q000378:metabolism*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D008024:Ligands; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011485:Protein Binding; D019087:Selectins / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D008024:Ligands; D019087:Selectins; C502597:FUT7 protein, human; D005647:Fucosyltransferases; C515956:FUT6 protein, human
keywords: CD34+; NSG mice; cord blood hematopoietic stem cell transplantation; fucosyltransferase; selectin; selectin ligands
references.citation: Exp Hematol. 2012 Jun;40(6):445-56
references.pmid: 22306295
references.citation: Thromb Haemost. 2001 Sep;86(3):746-56
references.pmid: 11583304
references.citation: Biochem Biophys Res Commun. 1997 Aug 8;237(1):131-7
references.pmid: 9266844
references.citation: Glycobiology. 1998 Apr;8(4):321-7
references.pmid: 9499379
references.citation: J Biol Chem. 1994 May 20;269(20):14730-7
references.pmid: 8182079
references.citation: Perspect Biol Med. 1995 Winter;38(2):230-7
references.pmid: 7899057
references.citation: J Clin Invest. 2002 Aug;110(4):559-69
references.pmid: 12189250
references.citation: Blood. 2004 Nov 15;104(10):3091-6
references.pmid: 15280192
references.citation: Curr Opin Cell Biol. 2002 Oct;14(5):581-6
references.pmid: 12231353
references.citation: N Engl J Med. 2006 Apr 27;354(17):1813-26
references.pmid: 16641398
references.citation: Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14423-8
references.pmid: 9826716
references.citation: Blood. 2002 Nov 1;100(9):3175-82
references.pmid: 12384415
references.citation: Blood Rev. 2011 Nov;25(6):255-9
references.pmid: 21764191
references.citation: Bone Marrow Transplant. 1993 Mar;11(3):199-200
references.pmid: 8096776
references.citation: Glycobiology. 2001 Oct;11(10):119R-128R
references.pmid: 11588153
references.citation: Blood. 2005 Jan 15;105(2):567-75
references.pmid: 15367439
references.citation: Nat Med. 2008 Feb;14(2):181-7
references.pmid: 18193058
references.citation: Cell. 1996 Aug 23;86(4):643-53
references.pmid: 8752218
references.citation: J Clin Invest. 2002 Apr;109(7):939-50
references.pmid: 11927621
references.citation: Blood. 1996 Aug 1;88(3):795-802
references.pmid: 8704232