{"doi":"10.1126/sciadv.adg1222","title":"Engineered cocultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation","abstract":"Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia treatable with antiarrhythmic drugs; however, patient responses remain highly variable. Human induced pluripotent stem cell-derived atrial cardiomyocytes (iPSC-aCMs) are useful for discovering precision therapeutics, but current platforms yield phenotypically immature cells and are not easily scalable for high-throughput screening. Here, primary adult atrial, but not ventricular, fibroblasts induced greater functional iPSC-aCM maturation, partly through connexin-40 and ephrin-B1 signaling. We developed a protein patterning process within multiwell plates to engineer patterned iPSC-aCM and atrial fibroblast coculture (PC) that significantly enhanced iPSC-aCM structural, electrical, contractile, and metabolic maturation for 6+ weeks compared to conventional mono-/coculture. PC displayed greater sensitivity for detecting drug efficacy than monoculture and enabled the modeling and pharmacological or gene editing treatment of an AF-like electrophysiological phenotype due to a mutated sodium channel. Overall, PC is useful for elucidating cell signaling in the atria, drug screening, and modeling AF.","journal":"Science Advances","year":2024,"id":420175,"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":35,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9488,"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":758977,"name":"Yong Duk Han","orcid":null,"position":1,"is_corresponding":false},{"id":108382,"name":"Ashlin R. Michell","orcid":"0000-0002-7563-4345","position":2,"is_corresponding":false},{"id":663525,"name":"Olivia T Ly","orcid":"0000-0002-9658-9643","position":3,"is_corresponding":false},{"id":465132,"name":"Carlos G. Vanoye","orcid":"0000-0002-4935-1122","position":4,"is_corresponding":false},{"id":1211035,"name":"Emanuele Spanghero","orcid":"0000-0003-3891-1961","position":5,"is_corresponding":false},{"id":321394,"name":"Alfred L. George","orcid":"0000-0002-3993-966X","position":6,"is_corresponding":false},{"id":1049,"name":"Dawood Darbar","orcid":"0000-0002-4103-5977","position":7,"is_corresponding":false},{"id":383037,"name":"Salman R. Khetani","orcid":"0000-0002-5407-6743","position":8,"is_corresponding":false},{"id":758247,"name":"Grace E. Brown","orcid":"0000-0002-1071-0108","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T01:57:25.777459Z","pmid":"38241367","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":[]}