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. 2023 Mar 10;13:53. doi: 10.1186/s13578-023-01003-9

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© The Author(s) 2023

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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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