Fig. 6

Isl1 elimination induces transcriptomic and epigenetic changes altering the composition of the endocrine cell population in the developing pancreas. a Overview of study design. b Volcano plot showing differentially expressed genes between FACS-sorted pancreatic endocrine cells from Isl1CKO (n = 5) and control E14.5 embryos (n = 6) identified by RNA sequencing (Padj < 0.05 displayed as –log₁₀ and log₂ fold change − 1 and 0.585). Thresholds are indicated by dotted lines. Complete list of differentially expressed genes in Supplementary Dataset 1a. c A simplified schematic overview of the different pancreatic cell types represented in single cell RNA-seq [39] used as a reference for the cell type deconvolution of our bulk cell RNA-seq data. d The deconvolved cell type proportions in E14.5 endocrine population from our bulk RNA-seq data. The proportion of major cell types is shown as an average and per individual samples. Data are presented as mean ± SD, Unpaired t-test (****P < 0.0001, ***P = 0.0007). See also Additional file 1: Fig. S4. e Heatmaps represent the top 30 enriched genes in endocrine progenitors, and in α and β cells in Isl1CKO and control samples based on the transcriptome analyses (*indicates genes with ISL1 binding sites at their promoter regions identified by the ISL1 CUT&Tag-seq, see page 13). Complete list of genes in Supplementary Dataset 1b and 1c, and S2. f Heatmap representation of expression profiles of differentially expressed genes that have differences in H3K4me3 or H3K27me3 enrichment in their promoter regions (± 3 kb from the TSS) between control and Isl1CKO cells. Scale bar for RNA-seq data represents average values calculated from the ratio of rlog of the sample to average rlog of the row (all samples per gene). Scale bars for CUT&Taq-seq data represent average counts per million (cpm; > 25 cpm) per each group. g Genome track view of representative gene loci showing H3K4me3 (green), H3K27me3 (magenta), and negative antibody control IgG (grey) normalized read peaks. EPs, endocrine progenitors