Induced pluripotent stem cells (iPSCs) from diverse humans offer the potential to study human functional variation in controlled culture environments. A portion of this variation originates from an ancient admixture between modern humans and Neandertals, which introduced alleles that left a phenotypic legacy on individual humans today. Here, we show that a large iPSC repository harbors extensive Neandertal DNA, including alleles that contribute to human phenotypes and diseases, encode hundreds of amino acid changes, and alter gene expression in specific tissues. We provide a database of the inferred introgressed Neandertal alleles for each individual iPSC line, together with the annotation of the predicted functional variants. We also show that transcriptomic data from organoids generated from iPSCs can be used to track Neandertal-derived RNA over developmental processes. Human iPSC resources provide an opportunity to experimentally explore Neandertal DNA function and its contribution to present-day phenotypes, and potentially study Neandertal traits.

来自不同人类的诱导多能干细胞 (iPSC) 为在受控培养环境中研究人类功能变异提供了潜力。这种变异的一部分源于现代人类和尼安德特人之间的古老混合，这种混合引入了等位基因，这些等位基因给今天的人类个体留下了表型遗产。在这里，我们展示了一个大型 iPSC 存储库包含广泛的尼安德特人 DNA，包括导致人类表型和疾病的等位基因，编码数百种氨基酸变化，并改变特定组织中的基因表达。我们为每个单独的 iPSC 系提供了推断的尼安德特人渐渗等位基因的数据库，以及预测的功能变异的注释。我们还表明，iPSC 生成的类器官的转录组数据可用于跟踪发育过程中尼安德特人衍生的 RNA。人类 iPSC 资源提供了一个机会来通过实验探索尼安德特人 DNA 功能及其对当今表型的贡献，并有可能研究尼安德特人的性状。