{"doi":"10.7554/elife.95603","title":"Tead1 reciprocally regulates adult β-cell proliferation and function to maintain glucose homeostasis","abstract":"Summary Proliferative quiescence in β-cells is required to maintain functional competence. While this presents a significant hurdle in regenerative therapy for diabetes, the molecular underpinnings of this reciprocal relationship remain unclear. Here, we demonstrate that TEAD1, the transcription effector of the mammalian-Hippo pathway, drives developmental stage-specific β-cell proliferative capacity in conjunction with its functional maturation. TEAD1 promotes adult β-cell mature identity by direct transcriptional control of a network of critical β-cell transcription factors, including, Pdx1, Nkx6.1, and MafA, while its regulation of Cdkn2a maintains proliferative quiescence. Consequently, mice with either constitutive or inducible genetic deletion of TEAD1 in β-cells developed overt diabetes due to a severe loss of secretory function despite induction of proliferation. Furthermore, we show that TEAD1 has a similar regulatory role in human β-cells. Consistent with this function in β-cells, variants in TEAD1 have been associated with c-HOMA-B in American Indians. We propose that TEAD1 is an essential intrinsic molecular switch coordinating adult β-cell proliferative quiescence with mature identity and its differential modulation may be necessary to overcome the challenge of inducing proliferation with functional competence in human beta cells.","journal":"eLife","year":2024,"id":495431,"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":0.9498,"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":564347,"name":"Ruya Liu","orcid":"0000-0003-1986-6800","position":1,"is_corresponding":false},{"id":564348,"name":"Byung S. Kim","orcid":"0000-0003-4671-1935","position":2,"is_corresponding":false},{"id":1186524,"name":"Yiqun Zhang","orcid":"0000-0002-0784-3444","position":3,"is_corresponding":false},{"id":564349,"name":"Feng Li","orcid":"0000-0002-7063-9497","position":4,"is_corresponding":false},{"id":565258,"name":"Rajaganapti Jagannathan","orcid":null,"position":5,"is_corresponding":false},{"id":1057335,"name":"Ping Yang","orcid":"0000-0003-2375-0616","position":6,"is_corresponding":false},{"id":469765,"name":"Vinny Negi","orcid":"0000-0003-3120-6952","position":7,"is_corresponding":false},{"id":565259,"name":"Joseph Danvers","orcid":null,"position":8,"is_corresponding":false},{"id":564351,"name":"Eliana Melissa Perez-Garcia","orcid":"0000-0002-3185-9649","position":9,"is_corresponding":false},{"id":482938,"name":"Pradip Saha","orcid":"0000-0002-8505-0917","position":10,"is_corresponding":false},{"id":564352,"name":"Omaima M. Sabek","orcid":"0000-0003-0919-0093","position":11,"is_corresponding":false},{"id":13376,"name":"Chad J. Creighton","orcid":"0000-0002-6090-703X","position":12,"is_corresponding":false},{"id":63736,"name":"Cristian Coarfa","orcid":"0000-0002-4183-4939","position":13,"is_corresponding":false},{"id":7355,"name":"Mark O. Huising","orcid":"0000-0002-6594-2205","position":14,"is_corresponding":false},{"id":323901,"name":"Hung-Ping Shih","orcid":"0000-0003-3035-5841","position":15,"is_corresponding":false},{"id":250524,"name":"Rita Bottino","orcid":"0000-0003-1540-2996","position":16,"is_corresponding":false},{"id":329470,"name":"Ke Ma","orcid":"0000-0002-5206-1038","position":17,"is_corresponding":false},{"id":564353,"name":"Mousumi Moulik","orcid":"0009-0007-8705-4181","position":18,"is_corresponding":false},{"id":60611,"name":"Vijay Yechoor","orcid":"0000-0002-9981-6784","position":19,"is_corresponding":false},{"id":330423,"name":"Jeongkyung Lee","orcid":null,"position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T02:09:19.627139Z","pmid":null,"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":[]}