Extended Data Fig. 3: Validation of beta cell T2D-differential cCREs in snATAC-seq data from an independent cohort of donor islets.

(a) Clustering of chromatin accessibility profiles from HPAP human islet snATAC-seq data (non-diabetic, n = 13; pre-T2D, n = 2; T2D, n = 5). Nuclei are plotted using the first two UMAP components. Clusters are assigned cell type identities based on promoter accessibility of known marker genes (see Extended Data Fig. 3b). The number of nuclei for each cell type cluster is shown in parentheses. (b) Promoter chromatin accessibility in a 5 kb window around TSS for selected endocrine and non-endocrine marker genes for each profiled nucleus (alpha: GCG, beta: INS-IGF2, delta: SST, acinar: REG1A). (c) Heatmap showing chromatin accessibility at differential cCREs identified in Fig. 1e in HPAP snATAC-seq data. Columns represent beta cells from each donor (non-diabetic, n = 13; T2D, n = 5) and all non-diabetic and T2D donors with accessibility of peaks normalized by CPM (counts per million).