{"doi":"10.1161/circulationaha.123.065294","title":"The Macrophage Landscape Across the Lifespan of a Human Cardiac Allograft","abstract":"BACKGROUND: Much of our knowledge of organ rejection after transplantation is derived from rodent models. METHODS: We used single-nucleus RNA sequencing to investigate the inflammatory myocardial microenvironment in human pediatric cardiac allografts at different stages after transplantation. We distinguished donor- from recipient-derived cells using naturally occurring genetic variants embedded in single-nucleus RNA sequencing data. RESULTS: Donor-derived tissue resident macrophages, which accompany the allograft into the recipient, are lost over time after transplantation. In contrast, monocyte-derived macrophages from the recipient populate the heart within days after transplantation and form 2 macrophage populations: recipient MP1 and recipient MP2. Recipient MP2s have cell signatures similar to donor-derived resident macrophages; however, they lack signatures of pro-reparative phagocytic activity typical of donor-derived resident macrophages and instead express profibrotic genes. In contrast, recipient MP1s express genes consistent with hallmarks of cellular rejection. Our data suggest that recipient MP1s activate a subset of natural killer cells, turning them into a cytotoxic cell population through feed-forward signaling between recipient MP1s and natural killer cells. CONCLUSIONS: Our findings reveal an imbalance of donor-derived and recipient-derived macrophages in the pediatric cardiac allograft that contributes to allograft failure.","journal":"Circulation","year":2024,"id":426813,"datarank":0.42498200160843247,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.0,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8986,"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":846065,"name":"Diwakar Turaga","orcid":"0000-0003-2775-3320","position":1,"is_corresponding":false},{"id":628393,"name":"Gang Li","orcid":"0000-0001-9661-8304","position":2,"is_corresponding":false},{"id":1161594,"name":"Chang-Ru Tsai","orcid":"0000-0001-5672-1235","position":3,"is_corresponding":false},{"id":891591,"name":"J. Quinn","orcid":"0009-0002-9729-4887","position":4,"is_corresponding":false},{"id":270500,"name":"Yi Zhao","orcid":"0000-0002-9908-0084","position":5,"is_corresponding":false},{"id":1090270,"name":"Ruby Wilson","orcid":null,"position":6,"is_corresponding":false},{"id":1226303,"name":"Katherine Carlson","orcid":"0000-0002-2083-944X","position":7,"is_corresponding":false},{"id":491805,"name":"Jun Wang","orcid":"0000-0001-6874-9331","position":8,"is_corresponding":false},{"id":738802,"name":"Joseph A. Spinner","orcid":"0000-0001-9539-6252","position":9,"is_corresponding":false},{"id":1226304,"name":"Edward Hickey","orcid":"0009-0006-0947-604X","position":10,"is_corresponding":false},{"id":846066,"name":"Iki Adachi","orcid":"0000-0003-1121-4461","position":11,"is_corresponding":false},{"id":295762,"name":"James F. Martin","orcid":"0000-0002-7842-9857","position":12,"is_corresponding":false},{"id":318079,"name":"Xiao Li","orcid":"0000-0001-8527-4438","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:58:42.796720Z","pmid":"38344825","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":[]}