Extended Data Fig. 9: Transcriptional programs distinguishing the two beta cell subtypes.
(a) Genome browser tracks showing aggregate RNA and ATAC read density at representative genes positively regulated by HNF1A, HNF4A or HNF4G. Beta cell cCREs with binding sites for HNF1A, HNF4A and HNF4G are shown. (b) Genome browser tracks showing aggregate RNA and ATAC read density at representative genes positively regulated by NEUROD1, NFIA or TCF4. Beta cell cCREs with binding sites for NEUROD1, NFIA and TCF4 are shown.(a, b) All tracks are scaled to uniform 1 × 106 read depth, differential expressed genes between beta-1 and beta-2 are indicated by grey shaded boxes. (c) Box plots showing accessibility at HNF1A, HNF4A and HNF4G proximal cCREs in beta-1 and beta-2 cells. Genomic coordinates of promotor regions are shown in parentheses. (d) Bar plots showing expression of HNF1A, HNF4A and HNF4G in beta-1 and beta-2 cells. (e) Bar plots showing accessibility at NEUROD1, NFIA and TCF4 proximal cCREs in beta-1 and beta-2 cells. Proximal region of genes were shown in parentheses. (f) Bar plots showing expression of NEUROD1, NFIA, and TCF4 in beta-1 and beta-2. (c-f) Accessibility of peaks is normalized by CPM, gene expression is normalized by TPM. Data are shown as mean ± S.E.M., n = 20 donors, Two-sided paired t-test. (g) Genome browser tracks showing aggregate RNA and ATAC read density at HNF1A, HNF4A and HNF4G in beta-1 and beta-2 cells. Beta cell cCREs with binding sites for HNF1A, HNF4A and HNF4G are shown. (h) Genome browser tracks showing aggregate RNA and ATAC read density at NEUROD1, NFIA and TCF4 in beta-1 and beta-2 cells. Beta cell cCREs with binding sites for NEUROD1, NFIA and TCF4 are shown. (i) Genome browser tracks showing aggregate RNA and ATAC read density at HNF1A and TCF4 in beta-1 and beta-2 cells. Beta cell cCREs with binding sites for HNF1A and TCF4 are shown. All tracks are scaled to uniform 1 × 106 read depth.
