Academic Journal
Fucosylation enhances CD34⁺ hematopoietic stem cell homing and longevity via E-selectin-mediated adhesion and signaling.
| Τίτλος: | Fucosylation enhances CD34⁺ hematopoietic stem cell homing and longevity via E-selectin-mediated adhesion and signaling. |
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| Συγγραφείς: | Al-Amoodi AS; Bioscience Program, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia., Alghuneim AA; Bioscience Program, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia.; Current Address: Research and Innovation, King Faisal Specialist Hospital & Research Centre, Riyadh, 11211, Kingdom of Saudi Arabia., Malki JS; Bioscience Program, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia., Nozue S; Bioscience Program, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia., Li Y; Bioscience Program, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia., Kai J; Bioscience Program, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia., Zhang H; Analytical Chemistry Core Lab - Proteomics Unit, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia., Bensaddek D; Analytical Chemistry Core Lab - Proteomics Unit, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia., Abdel-Aziz AK; Bioscience Program, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia.; Current Address: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt., Habuchi S; Bioscience Program, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia., Merzaban JS; Bioscience Program, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia. jasmeen.merzaban@kaust.edu.sa. |
| Πηγή: | BMC cancer [BMC Cancer] 2026 Jan 29; Vol. 26 (1). Date of Electronic Publication: 2026 Jan 29. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: BioMed Central Country of Publication: England NLM ID: 100967800 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2407 (Electronic) Linking ISSN: 14712407 NLM ISO Abbreviation: BMC Cancer Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London : BioMed Central, [2001- |
| Ιατρικοί όροι (MeSH): | E-Selectin*/metabolism , Fucose*/metabolism , Hematopoietic Stem Cells*/metabolism , Hematopoietic Stem Cells*/cytology , Antigens, CD34*/metabolism, Fucosyltransferases/metabolism ; Fucosyltransferases/genetics ; Humans ; Animals ; Signal Transduction ; Mice ; Cell Adhesion ; Cell Movement ; Hematopoietic Stem Cell Transplantation ; Mice, SCID ; Glycosylation |
| Περίληψη: | BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a cornerstone treatment for blood disorders and hematological malignancies, although its efficacy is limited by inefficient stem cell homing to the bone marrow. We previously demonstrated that fucosylated HSC ligands interact with endothelial E-selectin to facilitate homing. However, the downstream consequences of modulating fucosylation in HSCs remain unclear. Here, we systematically characterized how enhancing or inhibiting fucosylation—via recombinant human fucosyltransferase 6 (FTVI) or 2-fluoro-L-fucose (2FF), respectively—affects migration, signaling, and engraftment of human granulocyte-colony stimulating factor-mobilized peripheral blood CD34⁺ (mPB-CD34⁺) cells. METHODS: Live-cell imaging under flow, phosphoproteomics, and transcriptomics were used to characterize rolling dynamics and intracellular signaling, and in vivo homing was assessed in immunodeficient xenograft mouse models. RESULTS: Fucosylation enhanced tether and sling formation, improved E-selectin binding, and increased homing to the bone marrow and spleen. FTVI-treated cells activated MAPK and PI3K/AKT/mTOR pathways and showed enriched Rho-GTPase signaling, associated with proliferation and migration. In contrast, 2FF-treated cells had impaired migration and reduced rolling efficiency. Long-term xenograft studies showed enhanced bone marrow engraftment/persistence of fucosylated cells without altering lineage output. CONCLUSION: Fucosylation critically modulates E-selectin interactions, migration, and intracellular signaling in HSCs. These findings highlight glycoengineering as a promising strategy to enhance HSC transplantation outcomes in cancer therapy. |
| Competing Interests: | Declarations. Ethics approval and consent to participate: All in vivo experimental procedures were conducted in accordance with the Guide for the Care and Use of Laboratory Animals (NIH Publication No. 85–23, revised 1996) and the Implementing Regulations of the Law of Ethics of Research on Living Creatures (Kingdom of Saudi Arabia National Committee of Bioethics, 3rd Edition). All protocols were approved by the King Abdullah University of Science and Technology (KAUST) Institutional Animal Care and Use Committee (IACUC) under protocol number 17IACUC20. Competing interests: The authors declare no competing interests. |
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| Contributed Indexing: | Keywords: E-selectin; Fucosylation; HSC migration; HSCT; MAPK; PI3K/AKT/mTOR; Rho-GTPase; Sialyl Lewis X; Translational glycobiology; glycoengineering |
| Substance Nomenclature: | 0 (E-Selectin) 28RYY2IV3F (Fucose) EC 2.4.1.- (Fucosyltransferases) 0 (Antigens, CD34) EC 2.4.1.65 (FUT6 protein, human) |
| Entry Date(s): | Date Created: 20260129 Date Completed: 20260627 Latest Revision: 20260813 |
| Update Code: | 20260813 |
| PubMed Central ID: | PMC12977762 |
| DOI: | 10.1186/s12885-026-15614-1 |
| PMID: | 41612247 |
| Βάση Δεδομένων: | MEDLINE |
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