{"doi":"10.1016/j.exphem.2024.104653","title":"BST2 facilitates activation of hematopoietic stem cells through ERK signaling","abstract":"The proinflammatory cytokine interferon gamma (IFNγ) is upregulated in a variety of infections and contributes to bone marrow failure through hematopoietic stem cell (HSC) activation and subsequent exhaustion. The cell-surface protein, bone marrow stromal antigen 2 (BST2), is a key mediator of this process, because it is induced upon IFN stimulation and required for IFN-dependent HSC activation. To identify the mechanism by which BST2 promotes IFN-dependent HSC activation, we evaluated its role in niche localization, immune cell function, lipid raft formation, and intracellular signaling. Our studies indicated that knockout (KO) of BST2 in a murine model does not disrupt immune cell responses to IFN-inducing mycobacterial infection. Furthermore, intravital imaging studies indicate that BST2 KO does not disrupt localization of HSCs relative to endothelial or osteoblastic niches in the bone marrow. However, using imaging-based flow cytometry, we found that IFNγ treatment shifts the lipid raft polarity of wild-type (WT) but not <i>Bst2<sup>−/−</sup></i> hematopoietic stem and progenitor cells (HSPCs). Furthermore, RNAseq analysis, reverse-phase protein array and western blot analysis of HSPCs indicate that BST2 promotes ERK1/2 phosphorylation during IFNγ-mediated stress. Overall, we find that BST2 facilitates HSC division by promoting cell polarization and ERK activation, thus elucidating a key mechanism of IFN-dependent HSPC activation. These findings inform future approaches in the treatment of cancer and bone marrow failure.","journal":"Experimental Hematology","year":2024,"id":469359,"datarank":0.22154232871123225,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.013598174543248631,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.013598174543248631,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":3,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1173567,"name":"Apoorva Thatavarty","orcid":"0000-0001-9828-6331","position":1,"is_corresponding":false},{"id":618708,"name":"Duy T. Le","orcid":"0000-0003-3399-1376","position":2,"is_corresponding":false},{"id":644125,"name":"Holly A. Hill","orcid":"0000-0003-3642-1897","position":3,"is_corresponding":false},{"id":311038,"name":"Youngjae Jeong","orcid":"0000-0003-2884-5702","position":4,"is_corresponding":false},{"id":1069717,"name":"Brian M. Ho","orcid":"0000-0003-1533-6263","position":5,"is_corresponding":false},{"id":618710,"name":"Paweł Kuś","orcid":"0000-0002-4367-9821","position":6,"is_corresponding":false},{"id":1303085,"name":"Trisha K. Wathan","orcid":null,"position":7,"is_corresponding":false},{"id":618709,"name":"Bailee Kain","orcid":"0000-0002-8407-9937","position":8,"is_corresponding":false},{"id":2210,"name":"Shixia Huang","orcid":"0000-0003-2878-4129","position":9,"is_corresponding":false},{"id":311043,"name":"Dongsu Park","orcid":"0000-0002-2570-3250","position":10,"is_corresponding":false},{"id":311044,"name":"Katherine Y. King","orcid":"0000-0002-5093-6005","position":11,"is_corresponding":false},{"id":311037,"name":"Marcus A. Florez","orcid":"0000-0003-3785-5902","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:05:28.027781Z","pmid":"39362577","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":[]}