{"entity": "researcher", "timestamp": "2026-07-20T21:50:55.013Z", "family": "Bacos", "given": "Karl", "initials": "K", "orcid": "0000-0002-2461-9073", "affiliations": ["Department of Clinical Sciences Malm\u00f6, Lund University Diabetes Centre, Scania University Hospital, Malm\u00f6, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/527a271d23de48f8937b489c43e9da1b.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/527a271d23de48f8937b489c43e9da1b"}}, "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"}, {"entity": "publication", "iuid": "afb960cb22864dd38a6d8ae590cc4341", "links": {"self": {"href": "https://publications.scilifelab.se/publication/afb960cb22864dd38a6d8ae590cc4341.json"}, "display": {"href": "https://publications.scilifelab.se/publication/afb960cb22864dd38a6d8ae590cc4341"}}, "title": "Evaluating cell-specific gene expression using single-cell and single-nuclei RNA-sequencing data from human pancreatic islets of the same donors.", "authors": [{"family": "Engstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Nilsson", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Ofori", "given": "Jones K", "initials": "JK", "orcid": "0000-0001-6484-1544", "researcher": {"href": "https://publications.scilifelab.se/researcher/31b7b1843fd94a99b488eaf653c6385b.json"}}, {"family": "Wierup", "given": "Nils", "initials": "N"}, {"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": "2025-10-16", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "15", "issue": "1", "pages": "36133", "issn-l": "2045-2322"}, "abstract": "Single-cell and single-nuclei RNA-sequencing (scRNA-seq and snRNA-seq) analyze cell-specific transcriptomes. However, only snRNA-seq applies to frozen biobanked samples. For human pancreatic islets, marker genes and reference-based cell type annotation methods are mainly from scRNA-seq datasets and may not be suitable for snRNA-seq. We compared human islet scRNA-seq and snRNA-seq data from the same donors (N = 4) and evaluated annotation methods by studying cell type composition and gene detection, and identified novel marker genes. We compared cell type annotations: (1) manual annotation based on identified marker genes, (2) reference-based annotation using Azimuth's scRNA-seq pancreasref dataset, or (3) Seurat's label transfer from the Human Pancreas Analysis Program (HPAP) scRNA-seq dataset. ScRNA-seq and snRNA-seq identified the same cell types, but predicted cell type proportions differed. Cell type proportion-differences between annotation methods were larger for snRNA-seq. Reference-based annotations generated higher cell type prediction and mapping scores for scRNA-seq than snRNA-seq. Manual annotation identified the novel snRNA-seq markers DOCK10, KIRREL3 (beta cells), STK32B (alpha cells), MECOM, AC007368.1 (acinar cells), LAMC2 and SLC28A3 (ductal cells), which improve snRNA-seq-based annotation. We confirmed ZNF385D as a snRNA-seq beta cell marker and ZNF385D silencing reduced insulin secretion. In conclusion, this study discovered novel snRNA-seq cell type marker genes in human pancreatic islets, and highlights the need for tailored snRNA-seq annotation strategies.", "doi": "10.1038/s41598-025-21595-1", "pmid": "41102292", "labels": {"Clinical Genomics Lund": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12533216"}, {"db": "pii", "key": "10.1038/s41598-025-21595-1"}], "notes": [], "created": "2025-10-30T13:58:54.553Z", "modified": "2025-11-13T17:36:11.555Z"}, {"entity": "publication", "iuid": "cf4eea7dc9114c88a4492dde1a35c646", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cf4eea7dc9114c88a4492dde1a35c646.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cf4eea7dc9114c88a4492dde1a35c646"}}, "title": "Genes with epigenetic alterations in human pancreatic islets impact mitochondrial function, insulin secretion, and type 2 diabetes", "authors": [{"family": "R\u00f6nn", "given": "Tina", "initials": "T", "orcid": "0000-0001-7622-800X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d24f13a3d6e4538a6584634beabe5d3.json"}}, {"family": "Ofori", "given": "Jones K", "initials": "JK", "orcid": "0000-0001-6484-1544", "researcher": {"href": "https://publications.scilifelab.se/researcher/31b7b1843fd94a99b488eaf653c6385b.json"}}, {"family": "Perfilyev", "given": "Alexander", "initials": "A", "orcid": "0000-0003-1136-8946", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d86c6fc2d684b4dbc93c2c66e4c4b88.json"}}, {"family": "Hamilton", "given": "Alexander", "initials": "A", "orcid": "0000-0001-5203-9220", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f077dfd61a44eddb403c972994cd3e7.json"}}, {"family": "Pircs", "given": "Karolina", "initials": "K", "orcid": "0000-0001-8281-4785", "researcher": {"href": "https://publications.scilifelab.se/researcher/070f9eb7abde403697f7e8ba0f9ac40e.json"}}, {"family": "Eichelmann", "given": "Fabian", "initials": "F", "orcid": "0000-0002-3975-5596", "researcher": {"href": "https://publications.scilifelab.se/researcher/810ca03b2e8c4adf888cf694facbb38a.json"}}, {"family": "Garcia-Calzon", "given": "Sonia", "initials": "S"}, {"family": "Karagiannopoulos", "given": "Alexandros", "initials": "A", "orcid": "0000-0001-8458-1065", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8c0cfd9fd9741729f91d5dd554c199d.json"}}, {"family": "Stenlund", "given": "Hans", "initials": "H", "orcid": "0000-0001-9943-296X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5259d6369f564651ace11d8bff689535.json"}}, {"family": "Wendt", "given": "Anna", "initials": "A"}, {"family": "Volkov", "given": "Petr", "initials": "P"}, {"family": "Schulze", "given": "Matthias B", "initials": "MB"}, {"family": "Mulder", "given": "Hindrik", "initials": "H"}, {"family": "Eliasson", "given": "Lena", "initials": "L", "orcid": "0000-0002-6467-5029", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b6567e3b86e42c8bb5ef008b665f2de.json"}}, {"family": "Ruhrmann", "given": "Sabrina", "initials": "S"}, {"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": "2023-12-12", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "14", "issue": "1", "pages": "8040", "issn-l": "2041-1723"}, "abstract": "Epigenetic dysregulation may influence disease progression. Here we explore whether epigenetic alterations in human pancreatic islets impact insulin secretion and type 2 diabetes (T2D). In islets, 5,584 DNA methylation sites exhibit alterations in T2D cases versus controls and are associated with HbA1c in individuals not diagnosed with T2D. T2D-associated methylation changes are found in enhancers and regions bound by \u03b2-cell-specific transcription factors and associated with reduced expression of e.g. CABLES1, FOXP1, GABRA2, GLR1A, RHOT1, and TBC1D4. We find RHOT1 (MIRO1) to be a key regulator of insulin secretion in human islets. Rhot1-deficiency in \u03b2-cells leads to reduced insulin secretion, ATP/ADP ratio, mitochondrial mass, Ca2+, and respiration. Regulators of mitochondrial dynamics and metabolites, including L-proline, glycine, GABA, and carnitines, are altered in Rhot1-deficient \u03b2-cells. Islets from diabetic GK rats present Rhot1-deficiency. Finally, RHOT1methylation in blood is associated with future T2D. Together, individuals with T2D exhibit epigenetic alterations linked to mitochondrial dysfunction in pancreatic islets.", "doi": "10.1038/s41467-023-43719-9", "pmid": "38086799", "labels": {"Swedish Metabolomics Centre": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10716521"}, {"db": "pii", "key": "10.1038/s41467-023-43719-9"}], "notes": [], "created": "2024-01-10T09:59:46.931Z", "modified": "2025-10-17T13:03:13.252Z"}]}