Induced pluripotent stem cells (iPSC) derived from healthy individuals are important controls for disease-modeling studies. Here we apply precision health to create a high-quality resource of control iPSCs. Footprint-free lines were reprogrammed from four volunteers of the Personal Genome Project Canada (PGPC). Multilineage-directed differentiation efficiently produced functional cortical neurons, cardiomyocytes and hepatocytes. Pilot users demonstrated versatility by generating kidney organoids, T lymphocytes, and sensory neurons. A frameshift knockout was introduced into MYBPC3 and these cardiomyocytes exhibited the expected hypertrophic phenotype. Whole-genome sequencing-based annotation of PGPC lines revealed on average 20 coding variants. Importantly, nearly all annotated PGPC and HipSci lines harbored at least one pre-existing or acquired variant with cardiac, neurological, or other disease associations. Overall, PGPC lines were efficiently differentiated by multiple users into cells from six tissues for disease modeling, and variant-preferred healthy control lines were identified for specific disease settings.

源自健康个体的诱导性多能干细胞（iPSC）是疾病建模研究的重要对照。在这里，我们应用精度运行状况来创建控制iPSC的高质量资源。来自加拿大个人基因组计划（PGPC）的四名志愿者对无足迹线进行了重新编程。多向定向分化有效地产生了功能性皮层神经元，心肌细胞和肝细胞。飞行员用户通过产生肾脏类器官，T淋巴细胞和感觉神经元证明了其多功能性。MYBPC3中引入了移码敲除这些心肌细胞表现出预期的肥大表型。PGPC系基于全基因组测序的注释揭示了平均20种编码变体。重要的是，几乎所有带注释的PGPC和HipSci品系都带有至少一个预先存在或获得的与心脏，神经或其他疾病相关的变异。总体而言，PGPC系被多个用户有效地分化为来自六个组织的细胞以进行疾病建模，并且针对特定疾病设置鉴定了变异体偏爱的健康对照系。