Figure 7. T5224 or loss of FOS rescues the function of CDKAL1−/− cells in SCID-beige mice carrying human cells.
(A) Human insulin GSIS at 10 weeks after transplantation of mutant cells compared to wildtype cells (wt). (B) GSIS secretion of SCID-beige mice carrying human cells after glucose stimulation 48 hours after treatment with 300 mg/kg T5224 or vehicle. (C and D) IPGTT (C) and AUC (D) of mice transplanted with CDKAL1−/− cells treated with 300 mg/kg T5224 or vehicle. (E) GSIS secretion of SCID-beige mice carrying human cells after glucose stimulation after treatment with T5224 or vehicle twice a week for four weeks. (F and G) IPGTT (F) and AUC (G) of mice transplanted with CDKAL1−/− cells treated with 300 mg/kg T5224 or vehicle twice a week for 4 weeks. (H) GSIS secretion of SCID-beige mice transplanted with CDKAL1−/− cells carrying scramble sgRNA or CDKAL1−/− cells carrying sgFOS. (I and J) IPGTT (I) and AUC (J) of mice transplanted with CDKAL1−/− cells carrying scramble sgRNA or CDKAL1−/− cells carrying sgFOS at 6 weeks after transplantation. n=8 mice for each condition. hESCs were differentiated using protocol 2. In GSIS assay, p values were calculated by one-way repeated measures ANOVA. In IPGTT assay, p values were calculated by two-way repeated measures ANOVA with a Bonferroni test for multiple comparisons between DMSO and T5224 treated conditions. p values were *p<0.05, ** p<0.01, ***p<0.001. See also Figure S7.