{"doi":"10.1016/j.cmet.2023.03.008","title":"Epigenetic dosage identifies two major and functionally distinct β cell subtypes","abstract":"The mechanisms that specify and stabilize cell subtypes remain poorly understood. Here, we identify two major subtypes of pancreatic β cells based on histone mark heterogeneity (β HI and β LO ). β HI cells exhibit ∼4-fold higher levels of H3K27me3, distinct chromatin organization and compaction, and a specific transcriptional pattern. β HI and β LO cells also differ in size, morphology, cytosolic and nuclear ultrastructure, epigenomes, cell surface marker expression, and function, and can be FACS separated into CD24 + and CD24 − fractions. Functionally, β HI cells have increased mitochondrial mass, activity, and insulin secretion in vivo and ex vivo . Partial loss of function indicates that H3K27me3 dosage regulates β HI /β LO ratio in vivo , suggesting that control of β cell subtype identity and ratio is at least partially uncoupled . Both subtypes are conserved in humans, with β HI cells enriched in humans with type 2 diabetes. Thus, epigenetic dosage is a novel regulator of cell subtype specification and identifies two functionally distinct β cell subtypes.","journal":"Cell Metabolism","year":2023,"id":319332,"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":56,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9414,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":882265,"name":"Luca Fagnocchi","orcid":"0000-0002-9551-5474","position":1,"is_corresponding":false},{"id":702999,"name":"Vanessa Wegert","orcid":null,"position":2,"is_corresponding":false},{"id":882266,"name":"Stefanos Apostle","orcid":"0000-0001-7257-7421","position":3,"is_corresponding":false},{"id":882275,"name":"Brooke Grimaldi","orcid":"0000-0003-0384-3348","position":4,"is_corresponding":false},{"id":634628,"name":"Tim Gruber","orcid":"0000-0001-6884-7046","position":5,"is_corresponding":false},{"id":882268,"name":"Ilaria Panzeri","orcid":"0000-0002-4139-8591","position":6,"is_corresponding":false},{"id":882270,"name":"Steffen Heyne","orcid":"0000-0002-9497-7538","position":7,"is_corresponding":false},{"id":1028103,"name":"Kira D. Höffler","orcid":"0000-0002-0837-1469","position":8,"is_corresponding":false},{"id":1028104,"name":"Victor Kreiner","orcid":"0000-0002-7784-9286","position":9,"is_corresponding":false},{"id":1028105,"name":"Reagan W. Ching","orcid":"0000-0001-7452-6177","position":10,"is_corresponding":false},{"id":1028860,"name":"Tess Tsai-Hsiu Lu","orcid":null,"position":11,"is_corresponding":false},{"id":1028106,"name":"Ayush Semwal","orcid":"0000-0002-7598-6834","position":12,"is_corresponding":false},{"id":702998,"name":"Ben K. Johnson","orcid":null,"position":13,"is_corresponding":false},{"id":281426,"name":"Parijat Senapati","orcid":"0000-0002-7324-1230","position":14,"is_corresponding":false},{"id":882273,"name":"Adelheid Lempradl","orcid":"0000-0002-2621-9532","position":15,"is_corresponding":false},{"id":281431,"name":"Dustin E. Schones","orcid":"0000-0001-7692-8583","position":16,"is_corresponding":false},{"id":288788,"name":"Axel Imhof","orcid":"0000-0003-2993-8249","position":17,"is_corresponding":false},{"id":14040,"name":"Hui Shen","orcid":"0000-0001-9767-4084","position":18,"is_corresponding":false},{"id":563239,"name":"J. Andrew Pospisilik","orcid":"0000-0002-9745-0977","position":19,"is_corresponding":false},{"id":882269,"name":"Erez Dror","orcid":"0000-0002-9923-7600","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-19T01:07:12.004111Z","pmid":"36948185","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":[]}