Fig. 2: Molecular pathways involved in hypoxia response of stem cell-derived islets.

a A uniform manifold approximation and projection (UMAP) visualization of SC-islets cultured in 2, 5, and 21% oxygen for 2 or 4 weeks, combining all the time points and all the conditions. Cells are colored according to their assigned cell type. b UMAP of cells colored according to acquisition time point. c UMAP of cells colored according to the oxygen level. d UMAP of cells colored according to the expression of endocrine-associated markers (SC-β, INS; SC-α, GCG; SC-enterochromaffin cells, TPH1). Colors in (d) are unique and refer to gene expression. a–d represent the same UMAP colored as indicated above. e The population ratios of SC-islets cultured in 2, 5, and 21% oxygen levels after 2 weeks (left) and 4 weeks (right). Vertical bars are colored according to their assigned cell type in (a). f The correlation map of expression profiles of the main cell types identified in (a). g Expression levels of cell markers across cell types identified in the SC-islet cell population under hypoxia. The shading indicates the mean expression of each gene in the group, and the diameter of dots denotes the percentage of cells expressing the gene. h KEGG pathway analysis of SC-β cells in response to hypoxia, upregulated pathways (blue) or downregulated pathways (red) in SC-β INS^high vs. SC-β INS^low cells. Gene Set Enrichment Analysis (GSEA) is applied to analyze KEGG pathways. Multiple comparison was adjusted by Benjamini-Hochberg method. i Heatmap of selected genes in the KEGG pathway analysis shown in (h).