{"doi":"10.1093/glycob/cwaa113","title":"<i>O</i>-Fucose and Fringe-modified NOTCH1 extracellular domain fragments as decoys to release niche-lodged hematopoietic progenitor cells","abstract":"Successful hematopoietic progenitor cell (HPC) transplant therapy is improved by mobilizing HPCs from the bone marrow niche in donors. Notch receptor-ligand interactions are known to retain HPCs in the bone marrow, and neutralizing antibodies against Notch ligands, Jagged-1 or Delta-like ligand (DLL4), or NOTCH2 receptor potentiates HPC mobilization. Notch-ligand interactions are dependent on posttranslational modification of Notch receptors with O-fucose and are modulated by Fringe-mediated extension of O-fucose moieties. We previously reported that O-fucosylglycans on Notch are required for Notch receptor-ligand engagement controlling hematopoietic stem cell quiescence and retention in the marrow niche. Here, we generated recombinant fragments of NOTCH1 or NOTCH2 extracellular domain carrying the core ligand-binding regions (EGF11-13) either as unmodified forms or as O-fucosylglycan-modified forms. We found that the addition of O-fucose monosaccharide or the Fringe-extended forms of O-fucose to EGF11-13 showed substantial increases in binding to DLL4. Furthermore, the O-fucose and Fringe-extended NOTCH1 EGF11-13 protein displayed much stronger binding to DLL4 than the NOTCH2 counterpart. When assessed in an in vitro 3D osteoblastic niche model, we showed that the Fringe-extended NOTCH1 EGF11-13 fragment effectively released lodged HPC cells with a higher potency than the NOTCH2 blocking antibody. We concluded that O-fucose and Fringe-modified NOTCH1 EGF11-13 protein can be utilized as effective decoys for stem cell niche localized ligands to potentiate HPC egress and improve HPC collection for hematopoietic cell therapy.","journal":"Glycobiology","year":2020,"id":115963,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":542786,"name":"Weihuan Wang","orcid":"0000-0002-1053-6859","position":1,"is_corresponding":false},{"id":542787,"name":"Marwah Albakri","orcid":"0000-0001-7700-9802","position":2,"is_corresponding":false},{"id":305871,"name":"Xiaoxing Yu","orcid":"0000-0002-1607-0973","position":3,"is_corresponding":false},{"id":543358,"name":"Gurnoor Majihail","orcid":null,"position":4,"is_corresponding":false},{"id":542788,"name":"Seunghwan Lim","orcid":"0000-0001-8920-0890","position":5,"is_corresponding":false},{"id":448022,"name":"Rachel K. LoPilato","orcid":null,"position":6,"is_corresponding":false},{"id":468475,"name":"Atsuko Ito","orcid":null,"position":7,"is_corresponding":false},{"id":360780,"name":"John J. Letterio","orcid":"0000-0003-0437-6323","position":8,"is_corresponding":false},{"id":331479,"name":"Robert S. Haltiwanger","orcid":"0000-0001-7439-9577","position":9,"is_corresponding":false},{"id":542789,"name":"Lan Zhou","orcid":"0000-0003-1291-534X","position":10,"is_corresponding":false},{"id":542785,"name":"Shuiliang Yu","orcid":"0000-0002-9685-7433","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:13:40.596604Z","pmid":"33351914","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}