Extended Data Fig. 4: Generation and characterization of MODY8 disease-specific hiPSCs.
From: Abnormal exocrine–endocrine cell cross-talk promotes β-cell dysfunction and loss in MODY8
a, MODY8 family pedigree. Solid symbols denote diabetes. NN, no mutation; NM, mutation. b, Outline of the episomal reprogramming approach. Details are given in the Methods section. c, Representative bright-field images of hiPSC colonies derived from family and non-family controls (Fam Ctr n = 4, and Non-Fam Ctr n = 4 independent clones) and from mutation carriers with or without diabetes (Mut + Dia+ n = 8, Mut+ Dia- n = 6 independent clones). Scale bar is 1 mm. d, Normal karyotype of hiPSCs derived from controls and MODY8 patients (Non-Fam Ctr n = 2, Fam Ctr n = 2, Mut+ Dia- n = 4, Mut+ Dia+ n = 4 biologically independent samples). e, DNA sequencing confirmed presence of c.1686delT deletion (asterisk) in hiPSCs derived from MODY8 patients (Non-Fam Ctr n = 2, Fam Ctr n = 2, Mut+ Dia- n = 4, Mut+ Dia+ n = 4 biologically independent samples). f, Immunostaining for pluripotency markers OCT4 (red), SOX2 (green), SSEA4 (red) in hiPSCs derived from controls and mutation carriers (Non-Fam Ctr n = 2, Fam Ctr n = 2, Mut+ Dia- n = 4, Mut+ Dia+ n = 4 biologically independent samples). Nuclei stained with DAPI (blue). Scale bar is 500 μm. g, Control and MODY8 hiPSCs formed teratoma approximately 13 weeks after implantation into immunodeficient mice. Non-Fam Ctr n = 3, Fam Ctr n = 3, Mut+ Dia- n = 4, Mut+ Dia+ n = 4 biologically independent samples. Data are presented as mean values ± SEM. The difference between control vs mutant lines is not significant. Two-tailed t-test. h, Control and mutant hiPSCs formed teratoma (approximately 2 cm diameter) after injection into right leg muscle of immunodeficient mice (Non-Fam Ctr n = 3, Fam Ctr n = 3, Mut+ Dia- n = 4, Mut+ Dia+ n = 4 biologically independent samples). i, Representative images of teratomas stained with hematoxylin and eosin (HE) (Non-Fam Ctr n = 3, Fam Ctr n = 3, Mut+ Dia- n = 4, Mut+ Dia+ n = 4 biologically independent samples). Arrows show differentiated tissues including neural rosettes (ectoderm), cartilage (mesoderm), epithelial tissue (endoderm). Scale bar 50 μm.
