Transcriptome profiling of trisomy 21 and euploid iPSC-derived hematopoietic progenitors expressing wtGATA1 or an amino-truncated isoform of GATA1, GATA1short (GATA1s).

We generated human induced pluripotent stem cells (iPSCs) from trisomy 21 (T21) and euploid patient tissues with and without GATA1 mutations causing exclusive expression of truncated GATA1, termed GATA1short (GATA1s). Transcriptome analysis comparing expression levels of genes in GATA1s vs. wtGATA1-expressing progenitors demonstrated that GATA1s impairs erythropoiesis and enhances megakaryopoiesis and myelopoiesis in both T21 and euploid contexts in the iPSC-model system. We analyzed the transcriptome of (i) T21 iPSC-derived heamtopoietic progenitors expressing wtGATA1 (6 replicates) or GATA1s (3 replicates), as well as of (ii) euploid iPSC-derived progenitors expressing wtGATA1 (2 replicates) or GATA1s (2 replicates).