Modeling Down syndrome AML by introducing disese-specific mutations in iPSCs

Down syndrome AML is characterized by the presence of the pathgnonomic mutation in GATA1, which cooperates with other somatic mutations. In this study, we utilzed iPSCs derived from Down syndrome individuals bearing trisomy 21 and introduced disease-specific mutations using CRISPR-Cas9. Hematopoeitic stem and progenitor cells (HSPCs) obtained by hematopoeitic differentiation of these iPSCs, and megakaryocytes generated from the HSPCs (by culturing in megakaryocyte-specific media) were used for RNA sequencing analysis. Overall design: Transcriptome profiles in HSPCs and megakaryocytes from trisomic iPSCs with or without disease-specific mutations.