Extended Data Fig. 10: Transcriptional programs changed in both beta cell subtypes in T2D.
(a) Heatmap showing chromatin accessibility at cCREs with differential accessibility in beta-1 cells from non-diabetic and T2D donors. Columns represent beta cells from each donor (non-diabetic, n = 11; pre-T2D, n = 8; T2D, n = 15) with accessibility of peaks normalized by CPM (counts per million). (b) Heatmap showing chromatin accessibility at cCREs with differential accessibility in beta-2 cells from non-diabetic and T2D donors. Columns represent beta cells from each donor (non-diabetic, n = 11; pre-T2D, n = 8; T2D, n = 15) with accessibility of peaks normalized by CPM. (c) Heatmap showing expression of genes negatively regulated by TFs (green) with higher activity in non-diabetic compared to T2D beta-1 cells (see Methods) and TFs (red) with lower activity in non-diabetic compared to T2D beta-1 cells (n = 6 non-diabetic, n = 8 pre-T2D, n = 6 T2D donors). Representative target genes of individual TFs are highlighted and classified by biological processes. Gene expression is normalized by TPM (transcripts per million). # denotes TFs with decreased or increased expression in T2D in both beta-1 and beta-2 cells. (d) Heatmap showing expression of genes negatively regulated by TFs (green) with higher activity in non-diabetic compared to T2D beta-2 cells (see Methods) and TFs (red) with lower activity in non-diabetic compared to T2D beta-2 cells (n = 6 non-diabetic, n = 8 pre-T2D, n = 6 T2D donors). Representative target genes of individual TFs are highlighted and classified by biological processes. Gene expression is normalized by TPM (transcripts per million). # denotes TFs with decreased or increased expression in T2D in both beta-1 and beta-2 cells. (e-g) Pearson correlation of expression levels between indicated TFs across pseudo-bulk RNA profiles from each beta cell subtype (40 dots in total: 20 donors including n = 6 non-diabetic, n = 8 pre-T2D, n = 6 T2D). The bands around the linear regression line represent the range of the 95% confidence interval. Two-sided Pearson test.
