Fig. 4: Comparative analysis of SC-islets and primary human islets shows differences in chromatin accessibility signatures associated with islet identity.
a, Schematic showing comparisons of SC-islet and primary human islets (47,566 cells from 5 independent biological samples; all 3 SC-islets, 2 representative primary islets). b, Pearson correlation analysis comparing cell types in SC-islets and primary islets using gene expression and ATAC promoter accessibility. C, Heat map highlighting and comparing identity (β, adult β, α, δ, PP and EC) associated gene expression and ATAC promoter accessibility of endocrine cells in SC-islets and primary islets. d, Heat map highlighting and comparing off-target identity (exocrine, hepatic, oesophagus, stomach, intestinal and pancreatic progenitor) associated gene expression and ATAC promoter accessibility in SC-islet cells and primary islet cells. e, ATAC plots comparing chromatin accessibility around the INS, GCG and SST genomic regions in β, α and δ cells from SC-islets and primary islets. f, ATAC peaks from SC-β cells and 1° β cells showing chromatin accessibility around β-cell identity marker, MAFA (top) and UCN3 (bottom). Peaks were linked and analysed to depict differences in the number of cis-regulatory elements. g, Volcano plots showing differential motif accessibility analysis (top) and differential gene expression analysis (bottom) comparing SC-β cells and primary β cells. Statistical significance was assessed by two-sided Wilcoxon rank sum test for RNA expression and two-sided logistic regression for motif chromatin accessibility. h, Bar graphs showing fold change differences between SC-β cells and primary β cells, showing gene expression and motif accessibility of identified transcription factors (TFs) associated with SC-β cells, primary β cells and SC-EC cells. SC, stem cell derived; EC, enterochromaffin cells; PH, polyhormonal cells; Mes, mesenchyme; Duc, ductal; PP, pancreatic polypeptide cells; Acin, acinar cells.
