Fig. 5: Genes and pathways upregulated in β cells during recovery reflect activation of intracellular signaling to promote proliferation.
a Experimental schematic showing sorting of islet-derived β cells, endothelial cells (ECs), and macrophages (MΦs) from βVEGF-A mice at baseline (No Dox), during VEGF-A induction/β cell loss (1wk Dox), and during VEGF-A normalization/β cell recovery (1wk WD). See also Supplementary Fig. 5b–e. b Normalized expression of selected genes known to function in β cell proliferation34,35,36,37 at No Dox (n = 4 biological replicates), 1wk Dox (n = 5), and 1wk WD (n = 3). Numbers listed in 1wk Dox and 1wk WD columns represent fold-change ≥2 or <−2 (p < 0.05) as compared to No Dox. Color scale corresponds to normalized expression values ranging from 0 (white) to ≥6000 (dark blue). c Selected differentially regulated pathways during β cell recovery (1wk WD vs. No Dox), as determined by Ingenuity Pathway Analysis (IPA). Total bar width represents z-score; colored fractions indicate percentage of pathway genes that are up (blue), down (orange), and unchanged (gray). Number of genes per category is also listed within or adjacent to bars. A full list of significantly regulated pathways (z-score ≥2 or ≤−2, p < 0.05) is provided in Supplementary Table 1. FGF fibroblast growth factor, HGF hepatocyte growth factor, ILK integrin-linked kinase, MAPK mitogen-activated protein kinase, NFAT nuclear factor of activated T cells, NF-kB nuclear factor kappa-light-chain-enhancer of activated B cells, PI3K phosphoinositide 3-kinase, PAK p21-activated kinase, TREM1 triggering receptor expressed on myeloid cells 1, VEGF vascular endothelial growth factor.
