DNA Methylation-Dependent Restriction of Tyrosine Hydroxylase Contributes to Pancreatic β-Cell Heterogeneity.

ABSTRACT: The molecular and functional heterogeneity of pancreatic β-cells is well recognized, but the underlying mechanisms remain unclear. Pancreatic islets harbor a subset of β-cells that co-express tyrosine hydroxylase (TH), an enzyme involved in synthesis of catecholamines that repress insulin secretion. Restriction of the TH+ β-cells within islets is essential for appropriate function in mice, such that a higher proportion of these cells corresponds to reduced insulin secretion. Here, we use these cells as a model to dissect the developmental control of β-cell heterogeneity. We define the specific molecular and metabolic characteristics of TH+ β-cells and show differences in their developmental restriction in mice and humans. We show that TH expression in β-cells is restricted by DNA methylati

SUBMITTER: Parveen N 

PROVIDER: S-EPMC10130487 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature