{"doi":"10.1016/j.stem.2024.08.007","title":"Human vascularized macrophage-islet organoids to model immune-mediated pancreatic β cell pyroptosis upon viral infection","abstract":"There is a paucity of human models to study immune-mediated host damage. Here, we utilized the GeoMx spatial multi-omics platform to analyze immune cell changes in COVID-19 pancreatic autopsy samples, revealing an accumulation of proinflammatory macrophages. Single-cell RNA sequencing (scRNA-seq) analysis of human islets exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coxsackievirus B4 (CVB4) viruses identified activation of proinflammatory macrophages and β cell pyroptosis. To distinguish viral versus proinflammatory-macrophage-mediated β cell pyroptosis, we developed human pluripotent stem cell (hPSC)-derived vascularized macrophage-islet (VMI) organoids. VMI organoids exhibited enhanced marker expression and function in both β cells and endothelial cells compared with separately cultured cells. Notably, proinflammatory macrophages within VMI organoids induced β cell pyroptosis. Mechanistic investigations highlighted TNFSF12-TNFRSF12A involvement in proinflammatory-macrophage-mediated β cell pyroptosis. This study established hPSC-derived VMI organoids as a valuable tool for studying immune-cell-mediated host damage and uncovered the mechanism of β cell damage during viral exposure.","journal":"Cell stem cell","year":2024,"id":419155,"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":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.909,"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":109208,"name":"Yuling Han","orcid":"0000-0002-6805-4094","position":1,"is_corresponding":false},{"id":109215,"name":"Tuo Zhang","orcid":"0000-0001-5396-918X","position":2,"is_corresponding":false},{"id":1208447,"name":"Xue Dong","orcid":"0000-0001-5243-6453","position":3,"is_corresponding":false},{"id":125569,"name":"Jian Ge","orcid":null,"position":4,"is_corresponding":false},{"id":1209118,"name":"Aadita Roy","orcid":null,"position":5,"is_corresponding":false},{"id":109212,"name":"Jiajun Zhu","orcid":"0000-0003-2357-267X","position":6,"is_corresponding":false},{"id":1208448,"name":"Tiankun Lu","orcid":"0000-0002-8483-2087","position":7,"is_corresponding":false},{"id":399382,"name":"J. Jeya Vandana","orcid":"0000-0002-1026-569X","position":8,"is_corresponding":false},{"id":1209119,"name":"Neranjan de Silva","orcid":null,"position":9,"is_corresponding":false},{"id":426939,"name":"Catherine C. Robertson","orcid":"0000-0002-1120-1786","position":10,"is_corresponding":false},{"id":109227,"name":"Jenny Xiang","orcid":"0000-0003-0484-2769","position":11,"is_corresponding":false},{"id":1201080,"name":"Chendong Pan","orcid":"0000-0003-3058-7247","position":12,"is_corresponding":false},{"id":1209120,"name":"Yanjie Sun","orcid":null,"position":13,"is_corresponding":false},{"id":75510,"name":"Jianwen Que","orcid":"0000-0002-6540-6701","position":14,"is_corresponding":false},{"id":109233,"name":"Todd Evans","orcid":"0000-0002-7148-9849","position":15,"is_corresponding":false},{"id":109220,"name":"Chengyang Liu","orcid":"0000-0002-5802-1547","position":16,"is_corresponding":false},{"id":702320,"name":"Wei Wang","orcid":"0000-0002-4848-7394","position":17,"is_corresponding":false},{"id":109221,"name":"Ali Naji","orcid":"0000-0002-6926-3306","position":18,"is_corresponding":false},{"id":19898,"name":"Stephen C.J. Parker","orcid":"0000-0001-8122-0117","position":19,"is_corresponding":false},{"id":103718,"name":"Robert E. Schwartz","orcid":"0000-0002-5417-5995","position":20,"is_corresponding":false},{"id":109234,"name":"Shuibing Chen","orcid":"0000-0002-6294-5187","position":21,"is_corresponding":false},{"id":226396,"name":"Liuliu Yang","orcid":"0000-0003-0121-4214","position":0,"is_corresponding":true}],"reference_count":119,"raw_metadata":null,"created_at":"2026-07-19T01:57:14.586331Z","pmid":"39232561","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":[]}