{"doi":"10.1172/jci157086","title":"Disrupting the DREAM complex enables proliferation of adult human pancreatic β cells","abstract":"Resistance to regeneration of insulin-producing pancreatic β cells is a fundamental challenge for type 1 and type 2 diabetes. Recently, small molecule inhibitors of the kinase DYRK1A have proven effective in inducing adult human β cells to proliferate, but their detailed mechanism of action is incompletely understood. We interrogated our human insulinoma and β cell transcriptomic databases seeking to understand why β cells in insulinomas proliferate, while normal β cells do not. This search reveals the DREAM complex as a central regulator of quiescence in human β cells. The DREAM complex consists of a module of transcriptionally repressive proteins that assemble in response to DYRK1A kinase activity, thereby inducing and maintaining cellular quiescence. In the absence of DYRK1A, DREAM subunits reassemble into the pro-proliferative MMB complex. Here, we demonstrate that small molecule DYRK1A inhibitors induce human β cells to replicate by converting the repressive DREAM complex to its pro-proliferative MMB conformation.","journal":"Journal of Clinical Investigation","year":2022,"id":246674,"datarank":0.5456379239589579,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"self_citation_contribution":0.5456379239589579,"citation_network_contribution":0.0,"self_endowment_contribution":0.5456379239589579,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":316424,"name":"Esra Karaköse","orcid":"0000-0002-6940-5909","position":1,"is_corresponding":false},{"id":5805,"name":"Carmen Argmann","orcid":"0000-0002-1110-8012","position":2,"is_corresponding":false},{"id":381006,"name":"Huan Wang","orcid":"0000-0001-5628-5250","position":3,"is_corresponding":false},{"id":883347,"name":"Metodi Balev","orcid":"0009-0003-9242-0802","position":4,"is_corresponding":false},{"id":695191,"name":"Rachel Brody","orcid":"0000-0001-9280-517X","position":5,"is_corresponding":false},{"id":883348,"name":"Hembly G. Rivas","orcid":"0000-0002-9454-7810","position":6,"is_corresponding":false},{"id":255563,"name":"Xinyue Liu","orcid":"0000-0002-0934-4155","position":7,"is_corresponding":false},{"id":883980,"name":"Olivia Wood","orcid":null,"position":8,"is_corresponding":false},{"id":320809,"name":"Hongtao Liu","orcid":"0000-0002-7840-9661","position":9,"is_corresponding":false},{"id":678130,"name":"Lauryn Choleva","orcid":"0009-0007-4201-045X","position":10,"is_corresponding":false},{"id":329959,"name":"Dan Hasson","orcid":"0000-0001-7943-1636","position":11,"is_corresponding":false},{"id":329958,"name":"Emily Bernstein","orcid":"0000-0001-6533-8326","position":12,"is_corresponding":false},{"id":136624,"name":"Joao A. Paulo","orcid":"0000-0002-4291-413X","position":13,"is_corresponding":false},{"id":381015,"name":"Donald K. Scott","orcid":"0000-0002-1414-9223","position":14,"is_corresponding":false},{"id":381016,"name":"Luca Lambertini","orcid":"0000-0003-3326-219X","position":15,"is_corresponding":false},{"id":270590,"name":"James A. DeCaprio","orcid":"0000-0002-0896-167X","position":16,"is_corresponding":false},{"id":310886,"name":"Andrew F. Stewart","orcid":"0000-0001-7866-5959","position":17,"is_corresponding":false},{"id":320850,"name":"Peng Wang","orcid":"0000-0002-9031-9861","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:23:48.622830Z","pmid":"35700053","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":[]}