Genomic integrity of human pluripotent stem cells (hPSCs) is essential for research and clinical applications. However, genetic abnormalities can accumulate during hPSC generation and routine culture and following gene editing. Their occurrence should be regularly monitored, but the current assays to assess hPSC genomic integrity are not fully suitable for such regular screening. To address this issue, we first carried out a large meta-analysis of all hPSC genetic abnormalities reported in more than 100 publications and identified 738 recurrent genetic abnormalities (i.e., overlapping abnormalities found in at least five distinct scientific publications). We then developed a test based on the droplet digital PCR technology that can potentially detect more than 90% of these hPSC recurrent genetic abnormalities in DNA extracted from culture supernatant samples. This test can be used to routinely screen genomic integrity in hPSCs.

人类多能干细胞（hPSC）的基因组完整性对于研究和临床应用至关重要。但是，在hPSC生成，常规培养以及基因编辑后，遗传异常会累积。应定期监测它们的发生，但目前评估hPSC基因组完整性的检测方法并不完全适合此类常规筛查。为了解决这个问题，我们首先对100多个出版物中报告的所有hPSC遗传异常进行了大型荟萃分析，并鉴定出738例复发性遗传异常（即，至少在五种不同的科学出版物中发现了重叠的异常）。然后，我们开发了基于液滴数字PCR技术的测试，该测试可以潜在地检测从培养上清液样品中提取的DNA中90％以上的这些hPSC复发性遗传异常。该测试可用于常规筛选hPSC中的基因组完整性。