FIGURE 4.

Generation of OTC‐deficient patient‐derived hiPSC‐Heps. (A) Mutational analysis confirmed presence of OTC mutations in genomic DNA (gDNA) and mRNA of hiPSC‐Heps. OTCD_1 is a male patient, and his mutation was confirmed at the gDNA level. OTCD_2 is a female patient with one normal allele (c.274C) and one mutated allele (c.274T) at the gDNA level. The patient’s sequence on top shows a Y for the two pyrimidine bases C and T. At the mRNA level only, the mutated allele was expressed due to X‐chromosome inactivation–mediated silencing of the normal allele. (B) Scheme of X chromosome inactivation in epiblast and hiPSCs in female OTCD_2 patient. (C) Brightfield microscopy showing representative images of the differentiation process (for details see Supporting Methods) from hiPSCs to hiPSC‐Heps for Ctrl_1 and OTCD_1 and OTCD_2. Scale bars = 100 µM