{"entity": "researcher", "timestamp": "2026-07-16T11:39:34.998Z", "family": "Scisciola", "given": "Lucia", "initials": "L", "orcid": "0000-0003-3636-4298", "affiliations": ["Department of Advanced Medical and Surgical Sciences, University of Campania 'Luigi Vanvitelli', Naples, Italy."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/e332946efcac491b8953928cb46c0851.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/e332946efcac491b8953928cb46c0851"}}, "publications": [{"entity": "publication", "iuid": "9e0a3a071e494da1ae5ca45e7c048ec3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9e0a3a071e494da1ae5ca45e7c048ec3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9e0a3a071e494da1ae5ca45e7c048ec3"}}, "title": "Cell-specific DNA methylation in human alpha and beta cells regulates gene expression in type 2 diabetes.", "authors": [{"family": "Ofori", "given": "Jones K", "initials": "JK", "orcid": "0000-0001-6484-1544", "researcher": {"href": "https://publications.scilifelab.se/researcher/31b7b1843fd94a99b488eaf653c6385b.json"}}, {"family": "Ruhrmann", "given": "Sabrina", "initials": "S"}, {"family": "Lindstr\u00f6m", "given": "Axel", "initials": "A", "orcid": "0009-0008-1641-0406", "researcher": {"href": "https://publications.scilifelab.se/researcher/02c7aecdebce45cd87657f6756fe2977.json"}}, {"family": "Perfilyev", "given": "Alexander", "initials": "A"}, {"family": "Martin", "given": "Melina", "initials": "M"}, {"family": "Karagiannopoulos", "given": "Alexandros", "initials": "A", "orcid": "0000-0001-8458-1065", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8c0cfd9fd9741729f91d5dd554c199d.json"}}, {"family": "Scisciola", "given": "Lucia", "initials": "L", "orcid": "0000-0003-3636-4298", "researcher": {"href": "https://publications.scilifelab.se/researcher/e332946efcac491b8953928cb46c0851.json"}}, {"family": "Kost", "given": "Katja", "initials": "K"}, {"family": "J\u00f6nsson", "given": "Josefine", "initials": "J", "orcid": "0000-0003-0709-2828", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a4b2eb9eef5496eb27e76fc9fca120a.json"}}, {"family": "Nilsson", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Kantor", "given": "Boris", "initials": "B"}, {"family": "Dudenh\u00f6ffer-Pfeifer", "given": "Monika", "initials": "M"}, {"family": "Rots", "given": "Marianne G", "initials": "MG"}, {"family": "Wendt", "given": "Anna", "initials": "A"}, {"family": "R\u00f6nn", "given": "Tina", "initials": "T"}, {"family": "Eliasson", "given": "Lena", "initials": "L", "orcid": "0000-0002-6467-5029", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b6567e3b86e42c8bb5ef008b665f2de.json"}}, {"family": "Bacos", "given": "Karl", "initials": "K", "orcid": "0000-0002-2461-9073", "researcher": {"href": "https://publications.scilifelab.se/researcher/527a271d23de48f8937b489c43e9da1b.json"}}, {"family": "Ling", "given": "Charlotte", "initials": "C", "orcid": "0000-0003-0587-7154", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd7c1ea934034c4db99f31a5a9b04691.json"}}], "type": "journal article", "published": "2026-04-00", "journal": {"title": "Nat Metab", "issn": "2522-5812", "volume": "8", "issue": "4", "pages": "957-980", "issn-l": "2522-5812"}, "abstract": "Epigenome-wide studies of pancreatic islets provide valuable insights into type 2 diabetes (T2D) but lack methylomes from individual cell types. Here we show changes to alpha and beta cell-specific methylomes and transcriptomes from people with or without T2D, using whole-genome bisulfite sequencing and RNA sequencing. We discover 22,544 differentially methylated regions annotated to 7,975 genes in alpha versus beta cells, such as INS, GCG, PDX1 and PCSK1, with ~50% showing differential expression. CRISPR-dCas9-DNMT3A-based epigenetic editing increases INS and TH DNA methylation, while CRISPR-dCas9-TET1-based editing decreases GCG methylation, each altering INS, TH or GCG expression and content in beta cells. Pre-T2D/T2D-associated differentially methylated regions in alpha and beta cells overlap 12-18% of T2D-associated genome-wide association study candidates. Additionally, ONECUT2 is epigenetically upregulated in beta cells from people with pre-T2D/T2D and elevated in male Goto-Kakizaki rat islets. ONECUT2 overexpression in beta cells/islets downregulates gene sets impacting insulin secretion and glucose homeostasis, and reduces mitochondrial activity, ATP/ADP ratio and insulin secretion. We also provide 'alpha-beta-methylome' ( https://alpha-beta-methylome.serve.scilifelab.se/app/alpha-beta-methylome/ ), a resource exploring T2D, age and sex associations on methylation, highlighting cell-specific epigenetic regulation and dysfunctions contributing to T2D.", "doi": "10.1038/s42255-026-01498-9", "pmid": "42032109", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI Short read": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13121032"}, {"db": "pii", "key": "10.1038/s42255-026-01498-9"}], "notes": [], "created": "2026-06-24T14:02:31.698Z", "modified": "2026-06-24T14:02:32.023Z"}]}