High-Resolution Map of Pancreatic Cell DNA Methylation Ties ONECUT2 to Type 2 Diabetes

Overview

• The Nature Metabolism study, published Friday, delivers the first cell-specific DNA methylation atlas for human pancreatic alpha and beta cells.
• Analyzing hundreds of thousands of cells from 24 donors, the team found more than 22,000 regions across nearly 8,000 genes that differ between the two hormone-producing cell types.
• CRISPR epigenetic editing in cultured beta cells altered methylation near insulin and glucagon genes to pinpoint DNA regions that control hormone production.
• Beta cells from people with type 2 diabetes showed epigenetic upregulation of the transcription factor ONECUT2, which hindered cellular energy production and cut insulin release.
• The authors launched a web tool for researchers and say next tests will probe whether methylation edits can be reversed and sustained in living systems.