Extended Data Fig. 8: Differentiation of gene-edited hESCs and patient-derived hiPSCs to β-like cells.

a, FACS analysis of wild-type and mutant hESC lines differentiated to S6. + / + n = 4, +/1686delT n = 4, +/1698delA n = 3, +/1690_1702del n = 4, +/1683_1704del n = 4, 1686delT/1702delG n = 4 biologically independent samples. Data are presented as mean values ± SEM. No difference was detected in wild-type vs. each mutant line by two-tailed multiple t-test corrected using Holm-Sidak method. b, FACS analysis of control and mutant hiPSC lines differentiated to S6. Control n = 8, Mut+ Dia- n = 6, Mut+ Dia+ n = 6 biologically independent samples. Data are presented as mean values ± SEM. No difference was detected in control vs. Mut+ Dia- and vs. Mut+ Dia+ by two-tailed multiple t-test corrected using Holm-Sidak method. c, Immunostaining images, representative of three biologically independent samples, showing β-like cells for CPEP (green) and GCG (red). Nuclei stained with DAPI (blue). Scale bar is 500 μm. d, GSIS was performed by stimulating wild-type or mutant S6 cells with 1 mM low glucose (LG) or 20 mM high glucose (HG) for an hour. The stimulation index was calculated as the fold increase in human C-peptide release measured in 20 mM over 1 mM glucose. +/+ n = 4, +/1686delT n = 4, 1686delT/1702delG n = 4 biologically independent samples. Data are represented as median with 25% to 75% percentile box and min/max whisker plots. Two-tailed multiple t-tests followed by Holm Sidak’s multiple comparison test. e, Stimulation index of iPSC-derived β-like cells. Control n = 4, Mut+ Dia- n = 4, Mut+ Dia+ n = 4 biologically independent samples. Data are represented as median with 25% to 75% percentile box and min/max whisker plots. Two-tailed multiple t-tests followed by Holm Sidak’s multiple comparison test.