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. 2017 Sep 18;127(10):3835–3844. doi: 10.1172/JCI91761

Figure 3. Gene expression in human islets and juvenile grafts after treatment with Ex-4 and/or FK506.

Figure 3

(A and B) RNA-Seq analysis of PBS- or Ex-4–treated juvenile grafts (n = 3 grafts per treatment, 6-year-old donor). (A) Number of genes regulated by Ex-4 (≥1.5-fold) in juvenile grafts (Ex-4 vs. PBS); 1,115 genes are upregulated and 325 are downregulated by Ex-4 treatment. (B) Signaling pathways upregulated by Ex-4. (C) Genes of the NFATC family are expressed more highly in juvenile islets (n = 5 donors, age: 0.5, 1.2, 1.7, 3, and 4 years) than adult (n = 5 donors, age: 29, 43, 50, 53, and 60 years). The average expression level in juvenile islets is defined as 1.00 for each gene. (D) Schematic of transplantation and treatment with Ex-4 plus FK506. Two weeks after transplantation, a pump with PBS or Ex-4 was implanted, and a second pump with saline or FK506 was implanted in the last 2 weeks. Grafts were removed at 4 weeks. (E–G) Juvenile graft gene expression measured by qPCR. Ex-4 upregulates genes of the NFAT family (E), cell cycle regulators (F), and transcription factors (G), and the effects were diminished by FK506 (n = 5 graft samples per treatment from 0.2- and 6-year-old donors). The average expression level in PBS+saline–treated islets is defined as 1.00 for each gene. Error bars represent SEM. *P < 0.05, **P < 0.01, ***P < 0.001 vs. PBS+saline; †P < 0.05, ††P < 0.01, †††P < 0.001 vs. Ex-4+saline; no significant differences between PBS+FK506 and Ex-4+FK506. Unpaired 2-tailed Student’s t test or 1-way ANOVA followed by Newman-Keuls multiple-comparisons test (E–G) was used for analysis of statistical significance. See also Supplemental Figures 4 and 5.