Fibroblasts isolated from a skin biopsy of a healthy 46-year-old female were infected with Sendai virus containing the Yamanaka factors to produce transgene-free human induced pluripotent stem cells (iPSCs). CRISPR/Cas9 was used to generate isogenic cell lines with a gene dose-dependent deficiency of CDH13, a risk gene associated with neurodevelopmental and psychiatric disorders. Thereby, a heterozygous CDH13 knockout (CDH13^+/−) and a CDH13 null mutant (CDH13^−/−) iPSC line was obtained. All three lines showed expression of pluripotency-associated markers, the ability to differentiate into cells of the three germ layers in vitro, and a normal female karyotype.

从健康的46岁女性的皮肤活检组织中分离出的成纤维细胞被包含Yamanaka因子的仙台病毒感染，以产生无转基因的人类诱导性多能干细胞（iPSC）。CRISPR / Cas9被用于产生具有基因剂量依赖性缺陷CDH13的同基因细胞系，CDH13是与神经发育和精神疾病相关的风险基因。由此，获得杂合的CDH13敲除（CDH13 ^+/-）和CDH13无效突变体（CDH13 ^-/-）iPSC系。所有这三个系均显示多能性相关标志物的表达，体外分化为三个胚层的细胞的能力以及正常的雌性核型。