Fig. 6: Smo inactivation in δ-cells leads to enhanced conversion of α-cells β-cells.

a, Transgenes required for simultaneous δ-cell lineage tracing, Smo co-receptor downregulation and diphtheria toxin-induced β-cell ablation. b, Experimental design. c, Immunofluorescence staining of islets from δ-Smo-KO mice 1,5 months after diphtheria toxin-induced β-cell loss. Mice (δ-Smo-KO) display increased numbers of insulin⁺ and glucagon⁺ co-expressing cells compared to controls. d, Percentage of cells co-expressing insulin and glucagon in δ-Smo-KO mice. Treatment groups with no diphtheria toxin, n = 3 mice for all; diphtheria toxin treatment groups, n = 4, 6 and 4 for WT/WT, WT/fl and fl/fl mice, respectively. Two-tailed Mann–Whitney test; WT/fl versus WT/WT, P = 0.0095; fl/fl versus WT/WT, P = 0.0286. Horizontal bars indicate the mean. e, Transgenes for the simultaneous inactivation of Smo in α- and δ-cells, along with their lineage tracing, and for diphtheria toxin-induced β-cell ablation. f, Immunofluorescence staining of islets from α + δ-Smo-KO mice 1,5 months after diphtheria toxin treatment. g, Percentage of insulin⁺ and glucagon⁺ co-expressing cells traced with YFP. Mean ± s.e.m; two-tailed Mann–Whitney test, P = 0.84; n = 5 WT/fl mice, n = 4 fl/fl mice. *P < 0.5, **P < 0.01, ns, not significant. Experiments in c–f were repeated two independent times with similar results. Scale bars, 10 µm. See Supplementary Table 1n–p for the source data.