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 regula

SUBMITTER: Dror E 

PROVIDER: S-EPMC10160009 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature