Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK; Wellcome Trust - Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK; Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.
Cell Stem Cell. 2022 Dec 1;29(12):1685-1702.e22. doi: 10.1016/j.stem.2022.11.004.
Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC lines and deeply characterized their genetic properties using whole genome sequencing, their genomic stability upon CRISPR-Cas9-based gene editing, and their phenotypic properties including differentiation to commonly used cell types. These studies identified KOLF2.1J as an all-around well-performing iPSC line. We then shared KOLF2.1J with groups around the world who tested its performance in head-to-head comparisons with their own preferred iPSC lines across a diverse range of differentiation protocols and functional assays. On the strength of these findings, we have made KOLF2.1J and its gene-edited derivative clones readily accessible to promote the standardization required for large-scale collaborative science in the stem cell field.
人类诱导多能干细胞 (iPSC) 系是研究发育和疾病的有力工具，但由于系之间存在相当大的表型变异，因此难以复制关键发现并整合不同研究小组的数据。为了解决这个问题，我们对候选人类 iPSC 系进行了亚克隆，并使用全基因组测序、基于 CRISPR-Cas9 的基因编辑的基因组稳定性以及包括分化为常用细胞类型在内的表型特性对其遗传特性进行了深入表征。这些研究确定了 KOLF2.1J 是一种表现全面的 iPSC 系。然后，我们与世界各地的小组共享了 KOLF2.1J，他们在各种分化方案和功能测定中与自己首选的 iPSC 系进行了直接比较，以测试其性能。基于这些发现，我们已经使 KOLF2.1J 及其基因编辑衍生克隆易于获取，以促进干细胞领域大规模协作科学所需的标准化。
