For example, after grouping β-cells from each donor into quartiles based on their T2D pseudo indexes, downregulated T2D marker genes S100A10, FXYD2, and PPP1R1A and upregulated T2D marker genes CDKN2A, PDE4B, and SIX3 all demonstrated a clear trend of heterogeneity within the same donor (Fig. 4f, h), in both healthy and T2D donors. This evidence concerns the gene PDE4B and type 2 diabetes mellitus.