{"doi":"10.1016/j.stemcr.2021.08.001","title":"NOTCH-mediated ex vivo expansion of human hematopoietic stem and progenitor cells by culture under hypoxia","abstract":"[DXI]) has enabled ex vivo expansion of short-term HSPCs, but the effect on long-term repopulating hematopoietic stem cells (LTR-HSCs) remains uncertain. Here, we demonstrate that ex vivo culture of human adult HSPCs with DXI under low oxygen tension limits ER stress in LTR-HSCs and lineage-committed progenitors compared with normoxic cultures. A distinct HSC gene signature was upregulated in cells cultured with DXI in hypoxia and, after 21 days of culture, the frequency of LTR-HSCs increased 4.9-fold relative to uncultured cells and 4.2-fold compared with the normoxia + DXI group. NOTCH and hypoxia pathways intersected to maintain undifferentiated phenotypes in cultured HSPCs. Our work underscores the importance of mitigating ER stress perturbations to preserve functional LTR-HSCs in extended cultures and offers a clinically feasible platform for the expansion of human HSPCs.","journal":"Stem Cell Reports","year":2021,"id":176671,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":506464,"name":"Jian Fu","orcid":"0000-0002-5399-7831","position":1,"is_corresponding":false},{"id":391585,"name":"Heather D. Huntsman","orcid":null,"position":2,"is_corresponding":false},{"id":439201,"name":"Stefan Cordes","orcid":"0000-0003-0823-6504","position":3,"is_corresponding":false},{"id":268695,"name":"Fayaz Seifuddin","orcid":"0000-0003-3357-7888","position":4,"is_corresponding":false},{"id":227004,"name":"Luigi J. Alvarado","orcid":"0000-0002-7448-5384","position":5,"is_corresponding":false},{"id":720051,"name":"Patali S. Cheruku","orcid":null,"position":6,"is_corresponding":false},{"id":719411,"name":"Ayla Cash","orcid":"0000-0001-6622-5075","position":7,"is_corresponding":false},{"id":513495,"name":"Javier Traba","orcid":"0000-0002-7855-3540","position":8,"is_corresponding":false},{"id":314730,"name":"Yuesheng Li","orcid":"0000-0002-1393-3913","position":9,"is_corresponding":false},{"id":268694,"name":"Mehdi Pirooznia","orcid":"0000-0002-4210-6458","position":10,"is_corresponding":false},{"id":341076,"name":"Richard H. Smith","orcid":null,"position":11,"is_corresponding":false},{"id":340208,"name":"André Larochelle","orcid":"0000-0003-0685-2186","position":12,"is_corresponding":false},{"id":436183,"name":"Daisuke Araki","orcid":"0000-0001-5937-8882","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-18T23:47:23.605867Z","pmid":"34450041","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":[]}