{"doi":"10.1016/j.celrep.2025.116666","title":"DEC1 regulates human β cell functional maturation and circadian rhythm","abstract":"Stem cell-derived islet (SC-islet) organoids offer hope for cell replacement therapy in diabetes, but their immature function remains a challenge. Mature islet function requires the β cell circadian clock, yet how the clock regulates maturation is unclear. Here, we show that a circadian transcription factor specific to maturing SC-β cells, DEC1, regulates insulin responsiveness to glucose. SC-islet organoids form normally from DEC1-ablated human pluripotent stem cells, but their insulin release capacity and glucose threshold fail to increase during in vitro culture and upon transplant. This deficit reflects the downregulation of maturity-linked effectors of glucose utilization and insulin exocytosis, blunting glycolytic and oxidative metabolism, and is rescued by increasing metabolic flux. Moreover, DEC1 is needed to boost SC-islet maturity by synchronizing circadian glucose-responsive insulin secretion rhythms and clock machinery. Thus, DEC1 links circadian rhythms to human β cell maturation, highlighting the essential role of circadian control in generating fully functional SC-islet organoids.","journal":"Cell Reports","year":2025,"id":585168,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1498971,"name":"Bliss Zheng","orcid":null,"position":1,"is_corresponding":false},{"id":1498555,"name":"Zihan Gao","orcid":"0000-0003-4178-7957","position":2,"is_corresponding":false},{"id":1170296,"name":"Akshaya Biju","orcid":null,"position":3,"is_corresponding":false},{"id":1078206,"name":"Mai Liu","orcid":null,"position":4,"is_corresponding":false},{"id":1498556,"name":"Zhihui Cheng","orcid":"0009-0007-8768-3105","position":5,"is_corresponding":false},{"id":980647,"name":"Matthew Choi","orcid":"0000-0002-7849-1861","position":6,"is_corresponding":false},{"id":584484,"name":"Juan R. Alvarez‐Dominguez","orcid":"0000-0002-7136-2311","position":7,"is_corresponding":false},{"id":1359796,"name":"Sam Preza","orcid":"0000-0003-3612-3662","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T02:59:20.067334Z","pmid":"41385368","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":[]}