Here, Down syndrome-specific hiPSCs (DS1-hiPSCs and DS2-hiPSCs) were induced to differentiate to neural crest stem cells (NCSCs). We sequenced mRNA samples of DS1-NCSCs and DS2-NCSCs to generate the gene expression profiles of these cells. Overall design: mRNA samples of DS1-NCSCs and DS2-NCSCs were sequenced and analyzed.