{"doi":"10.1126/science.adn1629","title":"Transcripts of repetitive DNA elements signal to block phagocytosis of hematopoietic stem cells","abstract":"Macrophages maintain hematopoietic stem cell (HSC) quality by assessing cell surface Calreticulin (Calr), an “eat-me” signal induced by reactive oxygen species (ROS). Using zebrafish genetics, we identified Beta-2-microglobulin (B2m) as a crucial “don’t eat-me” signal on blood stem cells. A chemical screen revealed inducers of surface Calr that promoted HSC proliferation without triggering ROS or macrophage clearance. Whole-genome CRISPR-Cas9 screening showed that Toll-like receptor 3 (Tlr3) signaling regulated b2m expression. Targeting b2m or tlr3 reduced the HSC clonality. Elevated B2m levels correlated with high expression of repetitive element (RE) transcripts. Overall, our data suggest that RE-associated double-stranded RNA could interact with TLR3 to stimulate surface expression of B2m on hematopoietic stem and progenitor cells. These findings suggest that the balance of Calr and B2m regulates macrophage-HSC interactions and defines hematopoietic clonality.","journal":"Science","year":2024,"id":425687,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"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":702638,"name":"Joseph M. Collins","orcid":"0000-0002-5487-4294","position":1,"is_corresponding":false},{"id":354451,"name":"Song Yang","orcid":"0000-0002-3064-3141","position":2,"is_corresponding":false},{"id":1224446,"name":"Catherine Martinez","orcid":null,"position":3,"is_corresponding":false},{"id":822591,"name":"Ji Wook Kim","orcid":"0000-0002-9658-4703","position":4,"is_corresponding":false},{"id":993987,"name":"Chhiring Lama","orcid":null,"position":5,"is_corresponding":false},{"id":230389,"name":"Anna S. Nam","orcid":"0000-0003-4192-8916","position":6,"is_corresponding":false},{"id":248906,"name":"Clemens Alt","orcid":null,"position":7,"is_corresponding":false},{"id":85581,"name":"Charles P. Lin","orcid":"0000-0002-7450-627X","position":8,"is_corresponding":false},{"id":49576,"name":"Leonard I. Zon","orcid":"0000-0003-0860-926X","position":9,"is_corresponding":false},{"id":853304,"name":"Cecília Pessoa Rodrigues","orcid":"0000-0001-8617-6565","position":0,"is_corresponding":true}],"reference_count":90,"raw_metadata":null,"created_at":"2026-07-19T01:58:32.160975Z","pmid":"39264994","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":[]}