Fig. 3: Single-cell multiome sequencing of islets reveals diet-specific changes to beta-cell heterogeneity.

A Schematic representation of the workflow used for single nuclei multiome sequencing (ATAC + RNA) of pancreatic islets isolated from AL, CR and HFD mice after 2 months on diet. B Uniform Manifold Approximation and Projection (UMAP) of the integrated transcriptome and chromatin dataset. Data from a total of n = 18,741 islet cells from n = 2 mice per diet group. Different cell types are indicated by various colors and labels. Inset, donut plot with the total number of cells in each cell cluster. C UMAPs show the expression of cell marker genes. D Dot plot with relative expression of marker genes in alpha, beta, delta, gamma, acinar, endothelial, stellate, and macrophage cell clusters. E Genome tracks showing ATAC peaks for hormone markers: Gcg (alpha cell), Ins1 (beta cell), Sst (delta cell), and Ppy (gamma cell). F Heatmap showing the correlation between gene expression (RNA-seq) and chromatin accessibility (ATAC-seq) across the identified cell types. G Heatmap with the top differentially expressed genes (RNA-seq) and H top ATAC-seq peaks in transcriptional factors (TF) motifs in beta cells from AL, CR, and HFD mice. I Annotated node map with pathway enrichment analysis of differentially expressed genes and TF motifs in beta cells from CR mice. Analysis was performed using Metascape with an FDR < 0.05. J UMAP projection of beta cells and identified subclusters from AL, CR, and HFD mice. Beta cell populations were defined according to distinct transcriptional states. K Top marker genes from each beta-cell state. A was created with BioRender.com. and released under a Creative Commons Attribution-Non-Commercial NoDerivs 4.0 International license.