What the study found
The study found that DNA methylation, a chemical modification that can affect gene activity, differs between human pancreatic alpha and beta cells and is associated with type 2 diabetes. It also identified ONECUT2 as epigenetically upregulated in beta cells from people with pre-type 2 diabetes or type 2 diabetes.
Why the authors say this matters
The authors conclude that the findings highlight cell-specific epigenetic regulation and dysfunctions that contribute to type 2 diabetes. They also provide the alpha-beta-methylome resource for exploring methylation associations with type 2 diabetes, age, and sex.
What the researchers tested
The researchers compared methylomes, the full set of DNA methylation marks, and transcriptomes, the full set of RNA messages, from human alpha and beta cells from people with or without type 2 diabetes. They used whole-genome bisulfite sequencing, RNA sequencing, and CRISPR-dCas9-based epigenetic editing.
What worked and what didn't
They identified 22,544 differentially methylated regions across 7,975 genes in alpha versus beta cells, with about half showing different expression. Epigenetic editing increased INS and TH DNA methylation and decreased GCG methylation, and these edits altered INS, TH, or GCG expression and content in beta cells. Pre-type 2 diabetes/type 2 diabetes-associated differentially methylated regions overlapped 12% to 18% of type 2 diabetes genome-wide association study candidates, and ONECUT2 overexpression reduced gene sets linked to insulin secretion and glucose homeostasis as well as mitochondrial activity, ATP/ADP ratio, and insulin secretion.
What to keep in mind
The abstract does not describe detailed study limitations. It also presents associations and experimental effects within the specific cell types and models studied, so the findings should be read within that scope.
Key points
- DNA methylation patterns differed between human alpha and beta cells.
- 22,544 differentially methylated regions were identified across 7,975 genes.
- About half of the differentially methylated regions showed different gene expression.
- CRISPR-dCas9 epigenetic editing changed methylation and altered INS, TH, or GCG expression and content in beta cells.
- ONECUT2 was upregulated in beta cells from people with pre-type 2 diabetes or type 2 diabetes and its overexpression reduced insulin secretion-related measures.
Disclosure
- Research title:
- Cell-specific DNA methylation differs in alpha and beta cells in type 2 diabetes
- Authors:
- Jones K. Ofori, Sabrina Ruhrmann, Axel Lindström, Alexander Perfilyev, Melina Martin, Alexandros Karagiannopoulos, Lucia Scisciola, Katja Kost, Josefine Jönsson, Åsa Nilsson, Boris Kantor, Monika Dudenhöffer‐Pfeifer, Marianne G. Rots, Anna Wendt, Tina Rönn, Lena Eliasson, Karl Bacos, Charlotte Ling
- Institutions:
- Florida State University, Lund University, Lund University, Lund University, Lund University, Lund University, Lund University, Lund University, Lund University, Lund University, Lund University, Lund University, Lund University, Lund University, Lund University, Science for Life Laboratory, Science for Life Laboratory, Skåne University Hospital, Skåne University Hospital, Skåne University Hospital, Skåne University Hospital, Skåne University Hospital, Skåne University Hospital, Skåne University Hospital, Skåne University Hospital, Skåne University Hospital, University Medical Center Groningen, University of Campania "Luigi Vanvitelli", University of Copenhagen, University of Groningen
- Publication date:
- 2026-04-24
- OpenAlex record:
- View
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