Fig. 4: Beta cell heterogeneity arises during pancreas development. | Nature Communications

Fig. 4: Beta cell heterogeneity arises during pancreas development.

From: A multimodal cross-species comparison of pancreas development

Fig. 4: Beta cell heterogeneity arises during pancreas development.

a Detailed view of pig beta cells. (Top) UMAP of pig pancreas atlas with an inset showing a UMAP of the beta cells, colored by subclusters Beta,0 and Beta,1. (Bottom) Distribution of beta cell subclusters at each sampling age. b Volcano plot of differentially expressed genes between Beta,0 and Beta,1 (edgeR, FDR-corrected p-value < 0.05; Supplementary Data 6). Genes mentioned in core transcriptional regulatory circuits and identified in pathway analysis are highlighted. c CellOracle inferred GRN plots showing networks of the top 5 regulons from Beta,0 and Beta,1 clusters. d MEIS2 in silico KO simulation with CellOracle. (Left) UMAPs overlaid with the Palantir-pseudotime (top) or MEIS2 KO simulation (bottom) vector fields. (Middle) UMAP colored by MEIS2 KO perturbation score. (Right) Sankey diagram showing the effect of MEIS2 KO on cell fate transitions. e Immunofluorescence identification of MEIS2 positive and negative beta cells in wild-type pig pancreas and hiPSC-derived islet sections, scale bar 10 µm. Images are representative of 3 pig pancreas samples and 3 independent hiPSC differentiations. a-d: scRNA-seq of pancreatic cells from wild-type and INS-eGFP pigs. Detailed sample information is provided in Supplementary Data 1.

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