title: Fucose-deficient hematopoietic stem cells have decreased self-renewal and aberrant marrow niche occupancy.
abstract: BACKGROUND
  Modification of Notch receptors by O-linked fucose and its further elongation by the Fringe family of glycosyltransferase has been shown to be important for Notch signaling activation. Our recent studies disclose a myeloproliferative phenotype, hematopoietic stem cell (HSC) dysfunction, and abnormal Notch signaling in mice deficient in FX, which is required for fucosylation of a number of proteins including Notch. The purpose of this study was to assess the self-renewal and stem cell niche features of fucose-deficient HSCs.
  
  
  METHODS
  Homeostasis and maintenance of HSCs derived from FX(-/-) mice were studied by serial bone marrow transplantation, homing assay, and cell cycle analysis. Two-photon intravital microscopy was performed to visualize and compare the in vivo marrow niche occupancy by fucose-deficient and wild-type (WT) HSCs.
  
  
  RESULTS
  Marrow progenitors from FX(-/-) mice had mild homing defects that could be partially prevented by exogenous fucose supplementation. Fucose-deficient HSCs from FX(-/-) mice displayed decreased self-renewal capability compared with the WT controls. This is accompanied with their increased cell cycling activity and suppressed Notch ligand binding. When tracked in vivo by two-photon intravital imaging, the fucose-deficient HSCs were found localized farther from the endosteum of the calvarium marrow than the WT HSCs.
  
  
  CONCLUSIONS
  The current reported aberrant niche occupancy by HSCs from FX(-/-) mice, in the context of a faulty blood lineage homeostasis and HSC dysfunction in mice expressing Notch receptors deficient in O-fucosylation, suggests that fucosylation-modified Notch receptor may represent a novel extrinsic regulator for HSC engraftment and HSC niche maintenance.
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Myers
authors.forename: Yuanshuai
authors.initials: Y
authors.lastname: Huang
authors.forename: Lebing
authors.initials: L
authors.lastname: Wei
authors.forename: Quanjian
authors.initials: Q
authors.lastname: Yan
authors.forename: Alex
authors.initials: A
authors.lastname: Huang
authors.forename: Lan
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003198:Computer Simulation; D005260:Female; D005643:Fucose / Q000172:deficiency* / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011499:Protein Processing, Post-Translational / Q000502:physiology; D051880:Receptors, Notch / Q000378:metabolism; D055153:Stem Cell Niche / Q000166:cytology* / Q000378:metabolism
chemical_list: D051880:Receptors, Notch; D005643:Fucose; D006836:Hydro-Lyases; C044971:GDPmannose 4,6-dehydratase