Human stem cell resources are an inroad to Neandertal DNA functions

Abstract

Pluripotent stem cells from diverse humans offer the potential to study human functional variation in controlled culture environments. A portion of this variation originates from 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 repository of human induced pluripotent stem cells (iPSCs) harbors extensive Neandertal DNA, including most known functionally relevant Neandertal alleles present in modern humans. This resource contains Neandertal DNA that contributes to human phenotypes and diseases, encodes hundreds of amino acid changes, and alters gene expression in specific tissues. Human iPSCs thus provide an opportunity to experimentally explore the Neandertal contribution to present-day phenotypes, and potentially study Neandertal traits.