Discussion

Since human pluripotent stem cells can theoretically be differentiated into any cell type in the body, they are a potentially powerful tool for modelling human disease. Furthermore, mutations of interest can be introduced into human stem cells using gene editing technologies such as the CRISPR/Cas9 to generate powerful isogenic disease models. However, the genetic background of a cell line can dramatically alter the phenotypes seen in these models, potentially leading to misleading or conflicting results. Surprisingly, relatively little is known about the genetic background of most human embryonic stem cell lines. To address this issue, we performed whole genome sequencing of 121 human embryonic stem cell lines. We characterised the common variants that make some cell lines particularly suitable – and some less suitable – for modelling certain diseases. Furthermore, we identified highly penetrant disease-causing mutations that render certain cell lines less suitable for therapeutic transplantation. We will make this sequencing information freely available to serve as a resource to enable the rational selection of cell lines for disease modelling and transplantation.